No. Records Request
1 46 "ANGIOTENSIN-II"/ drug-effects
2 88739 HEART
3 20 #1 and #2
4 58 ATI
5 109088 RECEPTOR
6 6147 BLOCKER
7 1 ATI RECEPTOR BLOCKER
8 1500 AT1
9 109088 RECEPTOR
10 6147 BLOCKER
* 11 65 AT1 RECEPTOR BLOCKER

Record 1 of 65 - MEDLINE (R) 2001/01-2001/02
TI: Preserving target-organ function with candesartan cilexetil in patients
with hypertension.
AU: Zannad,-F
AD: Service de Cardiologie, Hopital Central, Nancy, France.
SO: Blood-Press-Suppl. 2000; 136-9
IS: 0803-8023
PY: 2000
LA: English
CP: NORWAY
AB: Epidemiological evidence suggests that reducing blood pressure alone in
hypertensive patients delaysthe onset of cardiovascular events without
necessarily preventing the progression of chronic target-organ disease,
such as end-stage renal failure and heart failure. Successful clinical
management of hypertensive patients will therefore not be possible unless
therapies are aimed both at the effective control of blood pressure and at
thepreservation of target-organ function. The new angiotensin II type I (AT1)
receptor blocker candesartan cilexetil has been shown to be effective in
reducing target-organ damage in animal models of hypertension, even at doses
that do not produce significant reductions in blood pressure. Protective effects
of candesartan cilexetil towards the heart and kidney have also been demonstrated
in the clinical studies that have been conducted to date.
Thus, candesartan cilexetil has been shown to induce regression of left ventricular
hypertrophy within 8-12 weeksof treatment and to improve renal haemodynamics, both
acutely and after 6 weeks of treatment in hypertensive patients. Furthermore,
in hypertensive patients with co-existent non-insulin-dependent diabetes mellitus and
microalbuminuria, 12 weeks of treatment with candesartan cilexetil, 8-16 mg,
significantly reduced urinary albumin excretion. Clinical evidence is therefore
accumulating that the antihypertensive efficacy and tolerability profile already
established for candesartan cilexetil is combined with the renal and cardioprotective
effects necessary for optimal management of hypertension.
MESH: *Antihypertensive-Agents-therapeutic-use; *Benzimidazoles-therapeutic-use;
*Biphenyl-Compounds-therapeutic-use; *Hypertension-drug-therapy; *Receptors,
-Angiotensin-antagonists-and-inhibitors
MESH: Hypertension-physiopathology; Hypertrophy,-Left-Ventricular-drug-therapy;
Kidney-drug-effects; Kidney-physiopathology
TG: Human
PT: Journal-Article; Review; Review,-Tutorial
SH: therapeutic-use; drug-therapy; physiopathology; drug-effects; antagonists-and-
inhibitors
RN: 0; 0; 0; 0; 0; 145040-37-5
NM: Antihypertensive-Agents; Benzimidazoles; Biphenyl-Compounds; Receptors,
-Angiotensin; angiotensin-II-type-1-receptor; TCV-116
SB: Index-Medicus
UD: 20010208
AN: 20511414
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 2 of 65 - MEDLINE (R) 2001/01-2001/02
TI: Achieving quality 24-h blood pressure control with candesartan cilexetil.
AU: Meredith,-P
AD: Department of Medicine and Therapeutics, University of Glasgow, UK.
SO: Blood-Press-Suppl. 2000; 123-6
IS: 0803-8023
PY: 2000
LA: English
CP: NORWAY
AB: Epidemiological evidence suggests that optimal blood pressure control requires strategies that
lower blood pressure consistently and fully throughout 24 h. In order to maximize compliance, ant
ihypertensive agents also need to be well tolerated and effective when administered at a convenient
once-daily dose. The new angiotensin II type 1 (AT1) receptor blocker candesartan binds tightly to, and
dissociates slowly from, the AT1-receptor and thereby provides long-lasting suppression of the
renin-angiotensin system. This is likely to explain its pronounced antihypertensive efficacy, which
is maintained smoothly over 24 h. The trough-to-peak ratio is a useful measure of the persistence of
antihypertensive efficacy at the end of the dosing interval. This ratio was found to be close to the
ideal of 1.0 for candesartan cilexetil, 8 and 16 mg, whereas it was 0.7 for the prototype AT1-receptor
blocker losartan, 50 mg. The antihypertensive effect of candesartan cilexetil, 16 mg, was also significantly
greater than that of losartan, 100 mg, as demonstrated by ambulatory blood pressure measurements
0-36 h after dosing and by clinic measurements 48 h after dosing. By controlling blood pressure well
beyond the normal dosing interval, candesartan cilexetil provides cardiovascular protection even
in those patients who may occasionally miss doses.
MESH: *Antihypertensive-Agents-therapeutic-use; *Benzimidazoles-therapeutic-use; *Biphenyl-Compounds-therapeutic-use; *Hypertension-drug-therapy; *Receptors,-Angiotensin-antagonists-and-inhibitors
MESH: Blood-Pressure-Monitoring,-Ambulatory; Hypertension-physiopathology; Time-Factors
TG: Human
PT: Journal-Article; Review; Review,-Tutorial
SH: therapeutic-use; drug-therapy; physiopathology; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 0; 145040-37-5
NM: Antihypertensive-Agents; Benzimidazoles; Biphenyl-Compounds; Receptors,-Angiotensin; angiotensin-II-type-1-receptor; TCV-116
SB: Index-Medicus
UD: 20010208
AN: 20511411
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 3 of 65 - MEDLINE (R) 2001/01-2001/02
TI: Inhibition of arterial thrombogenesis by quinapril but not losartan.
AU: Bavry,-A-A; Li,-D; Zander,-D-S; Phillips,-M-I; Mehta,-J-L
AD: Departments of Medicine, Pathology, and Physiology, University of Florida, College of Medicine and the VA Medical Center, Gainesville, Florida 32610, USA.
SO: J-Cardiovasc-Pharmacol-Ther. 2000 Apr; 5(2): 121-7
IS: 1074-2484
PY: 2000
LA: English
CP: UNITED-STATES
AB: The cardioprotective effect of angiotensin converting enzyme (ACE) inhibitors and angiotensin type I (AT1)
receptor blockers may relate to their antithrombotic effect. We determined the differential effects of
the ACE inhibitor quinapril and the AT1 receptor blocker losartan on arterial thrombus formation in the rat.
Sprague-Dawley rats were fed regular chow or chow mixed with low-dose quinapril (0. 6 mg/kg/day), high-dose
quinapril (1.2 mg/kg/day), or losartan (10 mg/kg/day) for 15 days. Abdominal aorta was exposed and wrapped
with Whatman paper impregnated with 29% FeCl(3) (ferric chloride). Time to occlusive thrombus formation and
weight of the thrombus were recorded. Aortic superoxide anion generation, platelet aggregation, plasma
angiotensin II levels, and morphology of the thrombus were also examined. Both losartan and quinapril caused
similar reductions in arterial pressure. Losartan did not affect the time to thrombus formation, whereas
quinapril (both low and high doses) delayed the time to thrombus formation (P<.01 vs control).
Weight of the thrombus was similar in all groups of rats. Platelet aggregation was inhibited by approximately
50 in both quinapril- and losartan-treated rats. The high-dose quinapril-treated rats showed markedly reduced
vascular superoxide anion generation compared with the control rats (P<.05). Plasma angiotensin II levels
were unaffected by quinapril treatment but were elevated 7-fold in losartan-treated rats (P <.001 vs. control rats).
The thrombi in the control rats consisted of platelet aggregates, fibrin, and red blood cells.
The intravascular platelet aggregates were much smaller in the quinapril-treated rats (P<.05 vs. control),
but were similar in control and losartan-treated rats. In conclusion, quinapril but not losartan prolongs
time to arterial thrombus formation and results in smaller platelet aggregates in the thrombus. Both quinapril
and losartan decrease platelet aggregation, but only quinapril decreases superoxide anion generation.
This effect on superoxide anion generation as well as mechanisms other than AT1 receptor blockade may underlie
the salutary effect of quinapril on arterial thrombogenesis.
MESH: *Angiotensin-Converting-Enzyme-Inhibitors-pharmacology; *Isoquinolines-pharmacology; *Losartan-pharmacology; *Thrombosis-prevention-and-control
MESH: Angiotensin-II-blood; Blood-Pressure-drug-effects; Dose-Response-Relationship,-Drug; Platelet-Aggregation-drug-effects; Rats-; Rats,-Sprague-Dawley; Superoxides-; Thrombosis-physiopathology
TG: Animal; Comparative-Study; Male; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: blood; pharmacology; drug-effects; physiopathology; prevention-and-control
RN: 0; 0; 11062-77-4; 11128-99-7; 114798-26-4; 82586-55-8
NM: Angiotensin-Converting-Enzyme-Inhibitors; Isoquinolines; Superoxides; Angiotensin-II; Losartan; quinapril
SB: Index-Medicus
UD: 20010201
AN: 20584489
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 4 of 65 - MEDLINE (R) 2001/01-2001/02
TI: Candesartan cilexetil and renal hemodynamics in hypertensive patients.
AU: Fridman,-K; Wysocki,-M; Friberg,-P; Andersson,-O-K
AD: Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. Katarina.Fridman@astrazeneca.com
SO: Am-J-Hypertens. 2000 Sep; 13(9): 1045-8
IS: 0895-7061
PY: 2000
LA: English
CP: UNITED-STATES
AB: This randomized, double-blind, placebo-controlled crossover study evaluated the effects of
the angiotensin II type 1 (AT1)-receptor blocker candesartan cilexetil on renal blood perfusion and
glomerular filtration in patients with primary hypertension with diastolic blood pressure of 100 to 114 mm Hg.
After a 4-week placebo run-in period, patients were randomized to receive either 16 mg candesartan cilexetil
or placebo once daily for 6 weeks, after which they were switched to the alternative treatment. At the end
of each period, 24 h after the last dose, renal assessments were made and the plasma renin activity, plasma
concentrations of angiotensin II, aldosterone, and catecholamines were measured. Compared with placebo,
candesartan cilexetil significantly reduced mean arterial pressure, by 8 mm Hg (95% confidence interval [CI], 3;12). Renal vascular resistance was significantly reduced by 0.03 mm Hg/mL min(-1) (95% CI, 0.01; 0.06). There was a small nonsignificant increase in renal plasma flow. The filtration fraction fell slightly from 0.24 to 0.22 (95% CI, -0.00, 0.04). As expected, angiotensin II concentrations and plasma renin activity were increased and the aldosterone concentrations were reduced. Catecholamine concentrations were unaffected. In conclusion, 6 weeks' treatment with 16 mg candesartan cilexetil once daily induced a reduction of renal vascular resistance and a trend toward increased renal plasma flow despite a reduction in mean arterial pressure. Because the glomerular filtration rate was maintained the filtration fraction was reduced, indicating a decreased glomerular capillary pressure.
MESH: *Antihypertensive-Agents-therapeutic-use; *Benzimidazoles-therapeutic-use; *Biphenyl-Compounds-therapeutic-use; *Hypertension-drug-therapy; *Hypertension-physiopathology; *Renal-Circulation-drug-effects
MESH: Adult-; Aged-; Blood-Pressure-drug-effects; Cross-Over-Studies; Double-Blind-Method; Hemodynamics-drug-effects; Hormones-blood; Middle-Age; Receptors,-Angiotensin-antagonists-and-inhibitors; Vascular-Resistance-drug-effects
TG: Female; Human; Male; Support,-Non-U.S.-Gov't
PT: Clinical-Trial; Journal-Article; Randomized-Controlled-Trial
SH: therapeutic-use; drug-effects; blood; drug-therapy; physiopathology; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 0; 0; 145040-37-5
NM: Antihypertensive-Agents; Benzimidazoles; Biphenyl-Compounds; Hormones; Receptors,-Angiotensin; angiotensin-II-type-1-receptor; TCV-116
SB: Index-Medicus
UD: 20010111
AN: 20434425
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 5 of 65 - MEDLINE (R) 2001/01-2001/02
TI: Ischemic cardiomyopathy and the cellular renin-angiotensin system.
AU: Anversa,-P; Leri,-A; Li,-B; Liu,-Y; Di-Somma,-S; Kajstura,-J
AD: New York Medical College, Department of Medicine, Valhalla, New York 10595, USA.
SO: J-Heart-Lung-Transplant. 2000 Aug; 19(8 Suppl): S1-11
IS: 1053-2498
PY: 2000
LA: English
CP: UNITED-STATES
AB: BACKGROUND: Ischemic cardiomyopathy produced by non-occlusive coronary artery constriction is characterized by left ventricular failure and right ventricular dysfunction, but whether the local renin-angiotensin system (RAS) is implicated in myocyte dysfunction and cell death remains unclear. METHODS: Changes in single-cell mechanics, the localization of the various constituents of RAS in the myocardium, and the effects of angiotensin II (Ang II) stimulation on myocyte performance and cell death were measured. RESULTS: Chronic ischemia is coupled with alterations in the mechanical properties and calcium (Ca2+) transients of the remaining viable myocytes. The abnormalities in myocyte mechanics consist of depression in peak shortening and velocity of shortening. Moreover, peak systolic Ca2+ is significantly decreased in the cells. In vitro stimulation with Ang II ameliorates myocyte function and systolic Ca2+. Additionally, adult myocytes express genes for renin, angiotensinogen, angiotensin-converting enzyme (ACE), and Ang II receptors. Renin, ACE, and Ang II receptors mRNAs increase under the setting of impaired coronary perfusion. Similarly, the percentage of myocytes containing renin, Ang I, and Ang II increases as well. In vitro studies of neonatal and adult ventricular myocytes indicate that Ang II triggers programmed myocyte cell death and this phenomenon is mediated by activation of the AT1 receptor sub-type. Importantly, the AT1-receptor blocker, losartan, completely inhibits apoptosis. CONCLUSIONS: These multiple observations are consistent with the notion that Ang II may exert 3 separate functions on the heart: (1) stimulation of myocyte hypertrophy, (2) amelioration of myocyte contractile performance, and (3) activation of the suicide program of myocytes.
MESH: *Angiotensin-II-metabolism; *Cardiomyopathy,-Congestive-metabolism; *Myocardial-Ischemia-metabolism; *Myocardium-metabolism; *Renin-Angiotensin-System
MESH: Apoptosis-drug-effects; Cardiomyopathy,-Congestive-etiology; Cardiomyopathy,-Congestive-pathology; Cell-Survival; Cells,-Cultured; Myocardial-Ischemia-pathology; Myocardium-pathology; Rats-; Sensitivity-and-Specificity; Ventricular-Dysfunction,-Left-physiopathology; Ventricular-Dysfunction,-Right-physiopathology
TG: Animal; Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article; Review; Review,-Tutorial
SH: metabolism; drug-effects; etiology; pathology; physiopathology
RN: 11128-99-7
NM: Angiotensin-II
CN: HL38132HLNHLBI; HL39902HLNHLBI; HL40561HLNHLBI
SB: Index-Medicus
UD: 20001228
AN: 20468696
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 6 of 65 - MEDLINE (R) 2001/01-2001/02
TI: Intrarenal angiotensin II augmentation in angiotensin II dependent hypertension.
AU: Navar,-L-G; Harrison-Bernard,-L-M
AD: Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
SO: Hypertens-Res. 2000 Jul; 23(4): 291-301
IS: 0916-9636
PY: 2000
LA: English
CP: JAPAN
AB: In several models of angiotensin II (ANG II) dependent hypertension, intrarenal ANG II levels increase to a much greater extent than the circulating levels even though the renal renin levels are decreased. The 2-kidney-1-clip (2K1C) Goldblatt rat model is particularly intriguing because hypertension develops in the presence of an intact kidney which would be expected to maintain sodium balance and protect against hypertension. Although the non-clipped kidney becomes renin depleted, it exhibits enhanced microvascular reactivity and increased tubular fractional sodium reabsorption. The non-clipped kidney ANG II content is either elevated or unchanged and proximal tubular fluid ANG II concentrations are not suppressed compared to the nanomolar concentrations found in normal rats. These results suggest that intrarenal ANG II content can be regulated independently of renal renin content. A similar hypertensive process occurs in rats infused chronically with low doses of ANG II. Renal ANG II content increases over 14 days to a greater extent than the circulating concentrations. Functionally, ANG II infused rats demonstrate reduced sodium excretion and marked suppression of pressure natriuresis. These ANG II dependent influences on kidney function contribute to the maintenance of hypertension. Renal augmentation of ANG II, hypertension, and suppressed sodium excretion are blocked by AT1 receptor blockers. To study the mechanisms responsible for intrarenal ANG II augmentation, we infused a different form of ANG II (Val5 ANG II), that can be separated from endogenous ANG II by HPLC. These results indicated that the increased renal ANG II content was due to accumulation of circulating ANG II in addition to continued production of endogenous ANG II. The renal accumulation of Val5-ANG II was markedly reduced by concomitant treatment with the AT1 receptor blocker, losartan. In addition, we found an unchanged overall ANG II-AT1 receptor protein which probably contributes to the maintained ANG II dependent influences. Collectively, the data support the concept that there is internalization of ANG II through an AT1 receptor mediated process and that some of the internalized ANG II is protected from degradation. The augmented intrarenal ANG II coupled with sustained levels of AT1 receptors contribute to the continued ANG II dependent suppression of renal function and sodium excretion thereby maintaining the hypertension.
MESH: *Angiotensin-II-analogs-and-derivatives; *Angiotensin-II-metabolism; *Hypertension-etiology; *Kidney-metabolism
MESH: Endosomes-metabolism; Hypertension-chemically-induced; Hypertension-metabolism; Intracellular-Membranes-metabolism; Receptors,-Angiotensin-metabolism; Renal-Artery-Obstruction-physiopathology
TG: Animal; Support,-U.S.-Gov't,-P.H.S.
PT: Lectures
SH: analogs-and-derivatives; metabolism; chemically-induced; etiology; physiopathology
RN: 0; 11128-99-7; 53-75-8
NM: Receptors,-Angiotensin; Angiotensin-II; angiotensin-II,-Asp(1)-Val(5)-
SB: Index-Medicus
UD: 20001115
AN: 20367892
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 7 of 65 - MEDLINE (R) 2000
TI: Favourable effects on arterial wave reflection and pulse pressure amplification of adding angiotensin II receptor blockade in resistant hypertension.
AU: Mahmud,-A; Feely,-J
AD: Department of Pharmacology and Therapeutics, Trinity College Dublin and Hypertension Clinic, St. James's Hospital, Dublin 8, Ireland.
SO: J-Hum-Hypertens. 2000 Sep; 14(9): 541-6
IS: 0950-9240
PY: 2000
LA: English
CP: ENGLAND
AB: OBJECTIVE: Angiotensin-converting enzyme (ACE) inhibitors have beneficial effects on arterial compliance and distensibility and favourably modify the arterial pressure waveform in hypertensive patients. The objective of our study was to explore the possible effects of adding an ATII AT1 receptor antagonist to an ACE inhibitor on augmentation pressure, a measure of arterial stiffness, and pulse pressure amplification in patients with poorly controlled essential hypertension. DESIGN AND METHODS: We studied a group of 18 patients with poorly controlled hypertension, despite at least three antihypertensive drugs including an ACE inhibitor, before, at 2 h and 2 weeks following the administration of 80 mg of valsartan, an ATII AT1 receptor antagonist. Haemodynamic responses were measured by cuff sphygmomanometry, arterial pulse-wave analysis and the pulse pressure gradient was calculated as the difference between the brachial pulse pressure (cuff sphygmomanometry) and derived aortic pulse pressure (arterial pulse wave analysis). RESULTS: Blood pressure decreased significantly (P<0.001) and the effect was more pronounced on central (aortic) pulse pressure than peripheral (brachial) pulse pressure. The pulse pressure amplification increased significantly (from 8+/-3 at baseline vs 12+/-7 at 2 h to 14+/-5 mm Hg at 2 weeks, P<0.01) and the augmentation pressure decreased from a baseline value of 21+/-8 to 11+/-7 at 2 h and 10+/-5 at 2 weeks, (P<0.01) following valsartan. CONCLUSION: The results of our study show that in a group of poorly controlled hypertensives, combining an ATII AT1 receptor blocker to an ACE inhibitor induced a significant fall in blood pressure. The decrease in blood pressure was accompanied by a decrease in augmentation pressure in the ascending aorta with a greater decrease in the central pulse pressure than in the peripheral, favourably increasing pulse pressure amplification between central and peripheral arteries. This effect on arterial stiffness and amplification suggests that combined angiotensin II blockade by adding an AT1 receptor blocker to an ACE inhibitor may have more beneficial effects on the blood pressure curve than simple blood pressure reduction.
CM: Comment In: J Hum Hypertens. 2000 Sep;14(9):533-5
MESH: *Angiotensin-Converting-Enzyme-Inhibitors-therapeutic-use; *Antihypertensive-Agents-therapeutic-use; *Arteries-physiopathology; *Blood-Pressure-drug-effects; *Hypertension-drug-therapy; *Hypertension-physiopathology; *Receptors,-Angiotensin-antagonists-and-inhibitors; *Tetrazoles-therapeutic-use; *Valine-analogs-and-derivatives; *Valine-therapeutic-use
MESH: Aged-; Aorta-drug-effects; Aorta-physiopathology; Arteries-drug-effects; Brachial-Artery-drug-effects; Brachial-Artery-physiopathology; Drug-Resistance; Drug-Therapy,-Combination; Heart-Rate-drug-effects; Middle-Age; Pulse-; Regional-Blood-Flow-drug-effects
TG: Female; Human; Male
PT: Journal-Article
SH: therapeutic-use; drug-effects; physiopathology; drug-therapy; antagonists-and-inhibitors; analogs-and-derivatives
RN: 0; 0; 0; 0; 0; 137862-53-4; 7004-03-7
NM: Angiotensin-Converting-Enzyme-Inhibitors; Antihypertensive-Agents; Receptors,-Angiotensin; Tetrazoles; angiotensin-II-type-1-receptor; valsartan; Valine
SB: Index-Medicus
UD: 20001218
AN: 20438063
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 8 of 65 - MEDLINE (R) 2000
TI: Study on COgnition and Prognosis in the Elderly (SCOPE): baseline characteristics.
AU: Hansson,-L; Lithell,-H; Skoog,-I; Baro,-F; Banki,-C-M; Breteler,-M; Castaigne,-A; Correia,-M; Degaute,-J-P; Elmfeldt,-D; Engedal,-K; Farsang,-C; Ferro,-J; Hachinski,-V; Hofman,-A; James,-O-F; Krisin,-E; Leeman,-M; de-Leeuw,-P-W; Leys,-D; Lobo,-A; Nordby,-G; Olofsson,-B; Opolski,-G; Prince,-M; Reischies,-F-M
AD: University of Uppsala, Department of Public Health, Clinical Hypertension Research, Sweden.
SO: Blood-Press. 2000; 9(2-3): 146-51
IS: 0803-7051
PY: 2000
LA: English
CP: NORWAY
AB: The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multi-centre, prospective, randomized, double-blind, parallel-group study. The primary objective of SCOPE is to assess the effect of the angiotensin II type 1 (AT1) receptor blocker, candesartan cilexetil 8-16 mg once daily, on major cardiovascular events in elderly patients (70-89 years of age) with mild hypertension (DBP 90-99 and/or SBP 160-179 mmHg). The secondary objectives of the study are to test the hypothesis that antihypertensive therapy can prevent cognitive decline (as measured by the Mini Mental State Examination, MMSE) and dementia, and to assess the effect of therapy on total mortality, myocardial infarction (MI), stroke, renal function, and hospitalization. A total of 4964 patients from 15 participating countries were recruited during the randomization phase of SCOPE, exceeding the target population of 4000. The mean age of the patients at enrolment was 76 years, the ratio of male to female patients was approximately 1:2, and 52% of patients were already being treated with an antihypertensive agent at enrolment. The majority of patients (88%) were educated to at least primary school level. At randomization, mean sitting blood pressure values were SBP 166 mmHg and DBP 90 mmHg, and the mean MMSE score was 28. Previous cardiovascular disease in the study population included myocardial infarction (4%), stroke (4%) and atrial fibrillation (4%). Men, more often than women, had a history of previous MI, stroke and atrial fibrillation. A greater percentage of men were smokers (13% vs 6% in women) and had attended university (11% vs 3% of women). Of the randomized patients, 21% were 80 years of age. In this age group smoking was less common (4% vs 10% for 70-79-year-olds) and fewer had attended university (4% vs 7% for 70-79-year-olds). The incidence of MI was similar in both age groups. However, stroke and atrial fibrillation had occurred approximately twice as frequently in the older patients. The patients' mean age at baseline was similar in the participating countries, and most countries showed the approximate 1:2 ratio for male to female patients. There was also little inter-country variation in terms of mean SBP, DBP or MMSE score. However, there was considerable regional variation in the percentage of patients on therapy prior to enrolment.
MESH: *Aging-psychology; *Antihypertensive-Agents-therapeutic-use; *Benzimidazoles-therapeutic-use; *Biphenyl-Compounds-therapeutic-use; *Cardiovascular-Diseases-prevention-and-control; *Cognition-physiology; *Receptors,-Angiotensin-antagonists-and-inhibitors
MESH: Aged-; Aged,-80-and-over; Cardiovascular-Diseases-epidemiology; Cardiovascular-Diseases-etiology; Cognition-Disorders-prevention-and-control; Dementia-prevention-and-control; Double-Blind-Method; Incidence-; Prognosis-; Risk-Factors; Sex-Characteristics
TG: Female; Human; Male
PT: Clinical-Trial; Journal-Article; Randomized-Controlled-Trial
SH: psychology; therapeutic-use; epidemiology; etiology; prevention-and-control; physiology; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 0; 145040-37-5
NM: Antihypertensive-Agents; Benzimidazoles; Biphenyl-Compounds; Receptors,-Angiotensin; angiotensin-II-type-1-receptor; TCV-116
SB: Index-Medicus
UD: 20001218
AN: 20312429
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 9 of 65 - MEDLINE (R) 2000
TI: Angiotensin II type 1 (AT1) receptor blockade in hypertensive women: benefits of candesartan cilexetil versus enalapril or hydrochlorothiazide.
AU: Malmqvist,-K; Kahan,-T; Dahl,-M
AD: Karolinska Institutet Danderyd Hospital, Division of Internal Medicine, Sweden. karin.malmqvist@med.ds.sll.se
SO: Am-J-Hypertens. 2000 May; 13(5 Pt 1): 504-11
IS: 0895-7061
PY: 2000
LA: English
CP: UNITED-STATES
AB: The aim of this large, randomized, double-blind, parallel-group study in hypertensive women was to compare the antihypertensive efficacy and effects on subjective symptoms and quality of life of the new angiotensin II type 1 (AT1) receptor blocker candesartan cilexetil, the angiotensin-converting enzyme inhibitor enalapril, and the diuretic hydrochlorothiazide (HCTZ). Women, aged 40 to 69 years, with a seated diastolic blood pressure (DBP) of 95 to 115 mm Hg, were randomized to candesartan cilexetil, 8 to 16 mg (n = 140), enalapril, 10 to 20 mg (n = 146), or HCTZ, 12.5 to 25 mg (n = 143), for 12 weeks; the higher doses were used if DBP was greater than 90 mm Hg after 6 weeks. Candesartan cilexetil lowered seated blood pressure by 17/11 and 19/11 mm Hg after 6 and 12 weeks of treatment, respectively. This reduction was greater (P < .01) than with enalapril (12/8 and 13/9 mm Hg) or HCTZ (12/7 and 13/8 mm Hg). The proportions of patients with controlled DBP (< 90 mm Hg) after 12 weeks of treatment with candesartan cilexetil, enalapril, or HCTZ were 60%, 51%, and 43%, respectively. Patients experienced less dry cough (P < 0.001) with candesartan cilexetil or HCTZ than with enalapril. No treatment differences were found in the incidence of dizziness and quality of life was well maintained in all groups. Compared with candesartan cilexetil and enalapril, HCTZ increased uric acid and decreased serum potassium (P < .001). In conclusion, candesartan cilexetil reduced blood pressure more effectively and was better tolerated than enalapril or HCTZ in women with mild to moderate hypertension.
MESH: *Angiotensin-Converting-Enzyme-Inhibitors-therapeutic-use; *Antihypertensive-Agents-therapeutic-use; *Benzimidazoles-therapeutic-use; *Biphenyl-Compounds-therapeutic-use; *Enalapril-therapeutic-use; *Hydrochlorothiazide-therapeutic-use; *Hypertension-drug-therapy; *Receptors,-Angiotensin-antagonists-and-inhibitors
MESH: Adult-; Aged-; Blood-Pressure-drug-effects; Diuretics,-Thiazide-therapeutic-use; Double-Blind-Method; Hypertension-blood; Hypertension-psychology; Middle-Age; Quality-of-Life
TG: Comparative-Study; Female; Human; Support,-Non-U.S.-Gov't
PT: Clinical-Trial; Journal-Article; Randomized-Controlled-Trial
SH: therapeutic-use; drug-effects; blood; drug-therapy; psychology; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 0; 0; 0; 145040-37-5; 58-93-5; 75847-73-3
NM: Angiotensin-Converting-Enzyme-Inhibitors; Antihypertensive-Agents; Benzimidazoles; Biphenyl-Compounds; Diuretics,-Thiazide; Receptors,-Angiotensin; angiotensin-II-type-1-receptor; TCV-116; Hydrochlorothiazide; Enalapril
SB: Index-Medicus
UD: 20001218
AN: 20284634
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 10 of 65 - MEDLINE (R) 2000
TI: AT1 receptor blockers--cost-effectiveness within the South African context.
AU: Anderson,-A-N; Wessels,-F; Moodley,-I; Kropman,-K
AD: Department of Pharmacy, University of the Witwatersrand, Johannesburg.
SO: S-Afr-Med-J. 2000 May; 90(5): 494-8
IS: 0038-2469
PY: 2000
LA: English
CP: SOUTH-AFRICA
AB: OBJECTIVES: Hypertension is a leading chronic disease in South Africa, Significant mortality results from this condition and from stroke and ischaemic heart disease in which hypertension plays a major role. The objective of this study was to evaluate the evidence for the clinically effective and cost-effective treatment of hypertension, given that the clinician has decided to administer an AT1 receptor blocker. METHODOLOGY: A cost-effectiveness analysis was undertaken from the perspective of the funder of health care in the private sector. A predetermined protocol defined the study scope, the comparators (candesartan, losartan, valsartan and irbesartan) and the inclusion criteria for peer-reviewed data. Data for the clinical efficacy of the comparators, measured as the reduction (mmHg) in sitting diastolic blood pressure (SDBP) achieved, were extracted, statistically assessed and reported. The combinability of the data from different clinical trials was confirmed using analyses of variance. A pharmacoeconomic model was developed by combining these clinical results with South African retail prices and testing the results at a 95% confidence level. RESULTS: Significant difference in clinical effectiveness was found among the comparators, with the following mean reductions in SDBP observed: candesartan 10.57, irbesartan 9.07, losartan 8.89 and valsartan 7.11 mmHg. Candesartan was found to be significantly more effective than losartan. Valsartan was found to be less effective than the other 3 comparators. No significant difference was found between irbesartan and either candesartan or losartan. The reduction in SDBP per R100 spent indicated that candesartan was more cost-effective than the other comparators, among which there were no significant differences. Incremental savings of R5.0 million annually could be achieved by the funders of private health care for every 100,000 successfully treated patients using candesartan. CONCLUSION: Significant differences exist in both the clinical and cost-effectiveness measures used in this study for the comparators. The findings from the analysis will be valuable in decision-making processes for both the funders and providers of health care. This analysis can be enhanced further by the inclusion of additional clinical benefits and long-term health outcomes when the relevant data become available.
MESH: *Angiotensin-Converting-Enzyme-Inhibitors-economics; *Antihypertensive-Agents-economics; *Hypertension-drug-therapy; *Meta-Analysis; *Receptors,-Angiotensin-antagonists-and-inhibitors
MESH: Angiotensin-Converting-Enzyme-Inhibitors-pharmacology; Angiotensin-Converting-Enzyme-Inhibitors-therapeutic-use; Antihypertensive-Agents-pharmacology; Antihypertensive-Agents-therapeutic-use; Cost-Benefit-Analysis; Economics,-Pharmaceutical; Sensitivity-and-Specificity; South-Africa
TG: Comparative-Study; Human; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: economics; pharmacology; therapeutic-use; drug-therapy; antagonists-and-inhibitors
RN: 0; 0; 0
NM: Angiotensin-Converting-Enzyme-Inhibitors; Antihypertensive-Agents; Receptors,-Angiotensin
SB: Index-Medicus
UD: 20001218
AN: 20360279
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 11 of 65 - MEDLINE (R) 2000
TI: Comparison of the AT1-receptor blocker, candesartan cilexetil, and the ACE inhibitor, lisinopril, in fixed combination with low dose hydrochlorothiazide in hypertensive patients.
AU: McInnes,-G-T; O'Kane,-K-P; Istad,-H; Keinanen-Kiukaanniemi,-S; Van-Mierlo,-H-F
AD: University Department of Medicine and Therapeutics Western Infirmary, Glasgow, UK.
SO: J-Hum-Hypertens. 2000 Apr; 14(4): 263-9
IS: 0950-9240
PY: 2000
LA: English
CP: ENGLAND
AB: AIM: To compare candesartan cilexetil and lisinopril in fixed combination with hydrochlorothiazide with respect to antihypertensive efficacy and tolerability. METHODS: This was a double-blind (double-dummy), randomised, parallel group comparison in patients with a mean sitting diastolic blood pressure 95-115 mm Hg on prior antihypertensive monotherapy. Treatments were candesartan cilexetil/hydrochlorothiazide 8/12.5 mg once daily (n = 237) and lisinopril/hydrochlorothiazide 10/12.5 mg once daily (n = 116) for 26 weeks. The primary efficacy variable was change in trough sitting diastolic blood pressure. RESULTS: Changes in mean sitting diastolic blood pressure did not differ significantly between the groups (mean difference 0.5 mm Hg; 95% confidence interval -1.6, 2.7, P = 0.20). No significant differences between the groups was found for other haemodynamic variables (sitting systolic blood pressure, standing blood pressure, sitting/erect heart rate, and proportion of responders and controlled patients). Both drugs were well tolerated but the proportion of patients with at least one adverse event was significantly greater in the lisinopril group (80% vs 69%, P = 0.020). The proportion of patients spontaneously reporting cough (23.1% vs 4.6%) and discontinuing therapy due to adverse events (12.0% vs 5.9%) was also higher in the lisinopril group compared with the candesartan cilexetil group. CONCLUSIONS: The fixed combinations of candesartan cilexetil and hydrochlorothiazide 8/12.5 mg and lisinopril and hydrochlorothiazide 10/12.5 mg once daily are equally effective as antihypertensive agents. The fixed combination containing candesartan cilexetil is better tolerated than that containing lisinopril.
MESH: *Angiotensin-Converting-Enzyme-Inhibitors-therapeutic-use; *Antihypertensive-Agents-therapeutic-use; *Benzimidazoles-therapeutic-use; *Biphenyl-Compounds-therapeutic-use; *Hydrochlorothiazide-administration-and-dosage; *Hypertension-drug-therapy; *Lisinopril-therapeutic-use; *Receptors,-Angiotensin-antagonists-and-inhibitors
MESH: Administration,-Oral; Adult-; Aged-; Aged,-80-and-over; Angiotensin-Converting-Enzyme-Inhibitors-administration-and-dosage; Antihypertensive-Agents-administration-and-dosage; Benzimidazoles-administration-and-dosage; Biphenyl-Compounds-administration-and-dosage; Blood-Pressure-drug-effects; Double-Blind-Method; Drug-Therapy,-Combination; Heart-Rate-drug-effects; Hypertension-metabolism; Hypertension-physiopathology; Lisinopril-administration-and-dosage; Middle-Age; Treatment-Outcome
TG: Comparative-Study; Female; Human; Male; Support,-Non-U.S.-Gov't
PT: Clinical-Trial; Journal-Article; Multicenter-Study; Randomized-Controlled-Trial
SH: administration-and-dosage; therapeutic-use; drug-effects; drug-therapy; metabolism; physiopathology; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 0; 0; 145040-37-5; 58-93-5; 83915-83-7
NM: Angiotensin-Converting-Enzyme-Inhibitors; Antihypertensive-Agents; Benzimidazoles; Biphenyl-Compounds; Receptors,-Angiotensin; angiotensin-II-type-1-receptor; TCV-116; Hydrochlorothiazide; Lisinopril
SB: Index-Medicus
UD: 20001218
AN: 20262802
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 12 of 65 - MEDLINE (R) 2000
TI: Dose-dependent effect of angiotensin II on human erythropoietin production.
AU: Freudenthaler,-S-M; Lucht,-I; Schenk,-T; Brink,-M; Gleiter,-C-H
AD: Klinische Pharmakologie, Universitat Gottingen, Germany.
SO: Pflugers-Arch. 2000 Apr; 439(6): 838-44
IS: 0031-6768
PY: 2000
LA: English
CP: GERMANY
AB: Current evidence suggests that angiotensin II may be involved in the regulation of renal erythropoietin (EPO) production. The present study assessed the role of angiotensin II (A II) in different doses in the control of EPO production in humans. In a parallel, randomized, placebo-controlled open design, 60 healthy male volunteers received a 6-h intravenous infusion of: placebo (placebo, electrolyte solution), a pressor dose of A II (1-3 microg/min; A II press), a combination of a pressor dose of A II and the selective AT1-receptor blocker losartan, 50 mg (A II press + L), a subpressor dose of A II (0.0375-0.15 microg/min; A II subpress) and a combination of a subpressor dose of A II and losartan (A II subpress + L). A II press treatment resulted in a significant increase of the maximum EPO concentration (CmaxEPO, 41% higher versus placebo) and the amount of EPO produced in 24 h (AUCEPO(0-24 h), 61% larger versus placebo), A II subpress treatment increased CmaxEPO (35% higher versus placebo) and AUC(EPO)(0-24 h) (34% larger versus placebo). A II press + L and A II subpress + L treatments did not significantly increase CmaxEPO and AUCEPO(0-24 h) compared to placebo. A II affects EPO production in a dose-dependent manner. The signal seems to be mediated via AT1-receptors. A II appears to be one modulator EPO production in humans.
MESH: *Angiotensin-II-pharmacology; *Erythropoietin-biosynthesis; *Vasoconstrictor-Agents-pharmacology
MESH: Adolescence-; Adult-; Angiotensin-II-blood; Antihypertensive-Agents-pharmacology; Area-Under-Curve; Dose-Response-Relationship,-Drug; Drug-Combinations; Erythropoietin-blood; Losartan-pharmacology; Osmolar-Concentration; Receptors,-Angiotensin-antagonists-and-inhibitors; Renin-blood; Time-Factors
TG: Human; Male
PT: Clinical-Trial; Journal-Article; Randomized-Controlled-Trial
SH: blood; pharmacology; biosynthesis; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 11096-26-7; 11128-99-7; 114798-26-4; EC 3.4.23.15
NM: Antihypertensive-Agents; Drug-Combinations; Receptors,-Angiotensin; Vasoconstrictor-Agents; Erythropoietin; Angiotensin-II; Losartan; Renin
SB: Index-Medicus
UD: 20001218
AN: 20244946
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 13 of 65 - MEDLINE (R) 2000
TI: Specific angiotensin II receptor blockage improves intestinal perfusion during graded hypovolemia in pigs.
AU: Aneman,-A; Svensson,-M; Broome,-M; Biber,-B; Petterson,-A; Fandriks,-L
AD: Department of Anesthesiology and Intensive Care, Goteborg University, Sweden.
SO: Crit-Care-Med. 2000 Mar; 28(3): 818-23
IS: 0090-3493
PY: 2000
LA: English
CP: UNITED-STATES
AB: OBJECTIVE: To investigate the potential of specific angiotensin II subtype 1 (AT1) receptor blockade to modify the mesenteric hemodynamic response to acute hypovolemia and retransfusion. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University-affiliated animal research laboratory. SUBJECTS: Fasted, anesthetized, ventilated, juvenile domestic pigs of both sexes. INTERVENTIONS: Acute, graded hypovolemia by 20% and 40% of the total estimated blood volume followed by retransfusion in control animals (CTRL; n = 10) and animals pretreated with the AT1 receptor blocker candesartan (CAND; n = 10). MEASUREMENTS AND MAIN RESULTS: Invasive monitoring of arterial and central venous blood pressures, cardiac output, portal venous blood flow, and jejunal mucosal blood flow. Blood gases were repeatedly analyzed to calculate oxygen delivery and consumption. Thirty minutes after each level of hypovolemia at 20% and 40%, cardiac output was decreased in CTRL animals from a baseline of 2.9 +/- 0.1 to 1.8 +/- 0.2 and 1.1 +/- 0.2 L/min, with no differences compared with CAND animals. Cardiac output was restored to 3.0 +/- 0.3 L/min 30 mins after retransfusion in CTRL animals, with no significant intergroup differences. Baseline portal venous blood flow (Q(MES)) and jejunal mucosal perfusion (PU(JEJ)) were greater in CAND animals compared with CTRL animals. During graded hypovolemia, CAND animals maintained Q(MES) and PU(JEJ) at significantly higher levels compared with CTRL animals, particularly after 40% hemorrhage (+221% and + 244%, respectively, relative to the mean values in CTRL animals). The same pattern was observed after retransfusion. Moreover, the calculated mesenteric critical oxygen delivery was significantly greater in CTRL animals (74 mL/min) compared with CAND animals (34 mL/min). No animals died in the CAND group, whereas four animals died during 40% hypovolemia or retransfusion in the CTRL group. CONCLUSIONS: Specific AT1 blockade before acute hypovolemia significantly ameliorated mesenteric and, in particular, jejunal mucosal hypoperfusion. In addition, cardiovascular stability was improved, and mortality in conjunction with acute hypovolemia and retransfusion could be completely avoided. These findings support a fundamental role of the renin-angiotensin system in the mesenteric response to acute hypovolemia and indicate a substantial interventional potential for candesartan in conjunction with circulatory stress.
CM: Comment In: Crit Care Med. 2000 Mar;28(3):898-9
MESH: *Benzimidazoles-therapeutic-use; *Hypovolemia-drug-therapy; *Intestinal-Mucosa-blood-supply; *Receptors,-Angiotensin-antagonists-and-inhibitors; *Splanchnic-Circulation-drug-effects; *Tetrazoles-therapeutic-use
MESH: Acid-Base-Equilibrium-drug-effects; Hemodynamics-drug-effects; Intestinal-Mucosa-drug-effects; Linear-Models; Prospective-Studies; Random-Allocation; Renin-Angiotensin-System-drug-effects; Swine-
TG: Animal; Female; Male; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: drug-effects; therapeutic-use; drug-therapy; blood-supply; antagonists-and-inhibitors
RN: 0; 0; 0; 139481-59-7
NM: Benzimidazoles; Receptors,-Angiotensin; Tetrazoles; CV-11974
SB: Abridged-Index-Medicus; Index-Medicus
UD: 20001218
AN: 20214509
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 14 of 65 - MEDLINE (R) 2000
TI: Roles of tyrosine kinase and protein kinase C in infarct size limitation by repetitive ischemic preconditioning in the rat.
AU: Tanno,-M; Tsuchida,-A; Nozawa,-Y; Matsumoto,-T; Hasegawa,-T; Miura,-T; Shimamoto,-K
AD: Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
SO: J-Cardiovasc-Pharmacol. 2000 Mar; 35(3): 345-52
IS: 0160-2446
PY: 2000
LA: English
CP: UNITED-STATES
AB: In this study, we examined the possibility that infarct-size limitation by repetitive preconditioning (PC) is achieved by activation of both protein kinase C (PKC) and tyrosine kinase. In addition, we assessed whether such kinase activation is triggered by angiotensin II type 1 (AT1) and alpha1-adrenergic receptors and whether sarcolemmal and mitochondrial adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels play roles as effectors of cardioprotection in the rat. Under pentobarbital anesthesia, myocardial infarction was induced by 20-min coronary occlusion and 3-h reperfusion in the rat. Infarct size was determined by tetrazolium and expressed as a percentage of area at risk (%IS/AR). PC with one cycle of 5-min ischemia/5-min reperfusion before 20-min ischemia significantly reduced %IS/AR from the control value of 49.4 +/- 2.0 to 35.4 +/- 2.8, and repetitive PC with two cycles of 5-min ischemia/5-min reperfusion further limited %IS/AR to 3.2 +/-0.9. Infarct-size limitation by single-cycle PC was completely abolished by a PKC inhibitor, staurosporine (100 microg/kg; %IS/ AR, 45.7 +/- 5.0). In contrast, the cardioprotection by repetitive PC was only partially blocked by staurosporine (%IS/AR, 19.8 +/- 2.4), another PKC inhibitor, polymyxin B (5 mg/kg; %IS/AR, 16.2 +/- 3.1), or a tyrosine kinase inhibitor, genistein (5 mg/kg; %IS/AR, 21.8 +/- 1.4). However, a combined injection of genistein and staurosporine additively inhibited protection of repetitive PC (%IS/AR, 36.4 +/- 1.7). Staurosporine, polymyxin B, or genistein alone did not modify %IS/AR in nonpreconditioned rat hearts. Infarct-size limitation by repetitive PC was not attenuated by pretreatment with a selective AT1-receptor blocker (CV11974, 10 mg/kg), prazosin (0.6 mg/kg; %IS/AR, 6.4 +/- 3.2 and 1.6 +/- 0.5, respectively). A selective blocker of mitochondrial K(ATP) channels, 5-hydroxydecanoate (3 mg/kg), completely abolished the cardioprotective effect (%IS/AR, 50.8 +/-3.5), but HMR1883 (3 mg/kg), a selective blocker of sarcolemmal K(ATP) channels, failed to inhibit the preconditioning effect (%IS/AR, 4.4 +/- 0.7). These findings suggest that repetition of PC provokes activation of both PKC and tyrosine kinase, leading to enhanced antiinfarct tolerance by opening of mitochondrial but not sarcolemmal K(ATP) channels. It is unlikely that activation of either AT1 or alpha1-adrenergic receptor alone is crucial to trigger preconditioning. Key Words: Tyrosine kinase-Genistein-Angiotensin II-alpha1-Adrenergic receptor-Sarcolemmal K(ATP) channel-Mitochondrial K(ATP) channel.
MESH: *Ischemic-Preconditioning,-Myocardial-methods; *Myocardial-Infarction-physiopathology; *Protein-Kinase-C-physiology; *Protein-Tyrosine-Kinase-physiology
MESH: Analysis-of-Variance; Blood-Pressure-drug-effects; Enzyme-Inhibitors-pharmacology; Genistein-pharmacology; Heart-Rate-drug-effects; Myocardial-Infarction-pathology; Myocardial-Infarction-prevention-and-control; Potassium-Channels-drug-effects; Protein-Kinase-C-antagonists-and-inhibitors; Protein-Tyrosine-Kinase-antagonists-and-inhibitors; Rats-; Rats,-Sprague-Dawley; Receptors,-Adrenergic,-alpha-drug-effects; Staurosporine-pharmacology
TG: Animal; Male
PT: Journal-Article
SH: drug-effects; pharmacology; methods; pathology; physiopathology; prevention-and-control; antagonists-and-inhibitors; physiology
RN: 0; 0; 0; 446-72-0; 62996-74-1; EC 2.7.1.-; EC 2.7.1.112
NM: Enzyme-Inhibitors; Potassium-Channels; Receptors,-Adrenergic,-alpha; Genistein; Staurosporine; Protein-Kinase-C; Protein-Tyrosine-Kinase
SB: Index-Medicus
UD: 20001218
AN: 20173351
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 15 of 65 - MEDLINE (R) 1999 Part B
TI: Differential effects of angiotensin II in the nucleus tractus solitarii of the rat--plausible neuronal mechanism.
AU: Kasparov,-S; Paton,-J-F
AD: Department of Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK. sergey.kasparov@bris.ac.uk
SO: J-Physiol. 1999 Nov 15; 521 Pt 1227-38
IS: 0022-3751
PY: 1999
LA: English
CP: ENGLAND
AB: 1. Cellular mechanisms of the actions of angiotensin II (ANGII) within the nucleus of the solitary tract (NTS) were studied using rat brain slices in 78 neurones recorded in the whole-cell configuration. Twenty-nine per cent of cells had an on-going activity and with only one exception these cells responded to tractus solitarii (TS) stimulation with a monophasic excitatory postsynaptic potential (EPSP). In approximately half of the silent cells, TS stimulation evoked an EPSP-inhibitory postsynaptic potential (IPSP) complex. 2. The ANGII (200 or 1000 nM) effect on TS-evoked EPSPs depended on the cell subpopulation. In cells with on-going activity, ANGII (1000 nM) increased evoked EPSP amplitude by +70 +/- 13 % (means +/- s.e.m., n = 5) but reduced it (200 and 1000 nM) in silent cells where both evoked EPSPs and IPSPs were present. ANGII either increased TS-evoked IPSP conductances in cells where they were detectable or revealed an evoked IPSP (200 nM ANGII: IPSP conductance increased from 70 +/- 29 to 241 +/- 34 pS; n = 11). All ANGII effects were prevented by the ANGII type 1 (AT1) receptor blocker losartan. Since 200 nM ANGII did not increase responses to iontophoretically applied GABA, the effect of ANGII on TS-evoked IPSPs may occur presynaptically. 3. The neurokinin type 1 (NK1) receptor antagonist CP-99,994 (5 microM) blocked the ANGII-induced increase in EPSPs but had no effect on TS-evoked IPSP potentiation by ANGII. 4. Thus, ANGII can potentiate both inhibitory and excitatory synaptic transmission within different subpopulations of NTS neurones. Potentiation of evoked EPSPs, but not of IPSPs, involves activation of NK1 receptors. The balance of these actions of ANGII could be reflex specific: for the baroreflex circuitry the inhibitory action might predominate while the peripheral chemoreceptor reflex may be facilitated due to enhanced excitatory transmission.
CM: Erratum In: J Physiol (Lond) 1999 Dec 15;521 Pt 3:761
MESH: *Angiotensin-II-pharmacology; *Solitary-Nucleus-drug-effects; *Solitary-Nucleus-physiology
MESH: Angiotensin-II-administration-and-dosage; Baroreflex-drug-effects; Baroreflex-physiology; Chemoreceptors-drug-effects; Chemoreceptors-physiology; Drug-Interactions; Electric-Stimulation; Excitatory-Postsynaptic-Potentials-drug-effects; Neurons-drug-effects; Neurons-physiology; Patch-Clamp-Techniques; Piperidines-administration-and-dosage; Rats-; Rats,-Sprague-Dawley; Receptors,-Neurokinin-1-antagonists-and-inhibitors; Solitary-Nucleus-cytology; Synaptic-Transmission-drug-effects; Synaptic-Transmission-physiology
TG: Animal; Female; In-Vitro; Male; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: administration-and-dosage; pharmacology; drug-effects; physiology; antagonists-and-inhibitors; cytology
RN: 0; 0; 11128-99-7; 136982-36-0
NM: Piperidines; Receptors,-Neurokinin-1; Angiotensin-II; CP-99994
SB: Index-Medicus
UD: 20001218
AN: 20030131
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 16 of 65 - MEDLINE (R) 1999 Part B
TI: Angiotensin II modulates conducted vasoconstriction to norepinephrine and local electrical stimulation in rat mesenteric arterioles.
AU: Gustafsson,-F; Holstein-Rathlou,-N-H
AD: Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark. finng@mfi.ku.dk
SO: Cardiovasc-Res. 1999 Oct; 44(1): 176-84
IS: 0008-6363
PY: 1999
LA: English
CP: NETHERLANDS
AB: OBJECTIVE: Localized application of a vasoconstricting agent onto the wall of an arteriole results not only in a local constriction of the vessel, but also in a conducted vasoconstriction which is detectable more than a millimeter upstream and downstream from the application site. We investigated the effect of intravenous infusion of angiotensin II (ANG II), losartan or methoxamine on conducted vasoconstriction to local application of norepinephrine (NE) or local electrical stimulation onto the surface of rat mesenteric arterioles in vivo. METHODS: In anesthetized male Wistar rats (n = 43) NE (0.1 mM) or a local depolarizing current was continuously applied onto mesenteric arterioles using micropipettes. Local and conducted vasoconstriction was measured using videomicroscopy. Conducted responses were measured 200-1000 microns upstream from the application site. RESULTS: Systemic infusion of ANG II (4 ng/min) raised mean arterial blood pressure by 6 +/- 2 mm Hg and increased the conducted but not the local vasoconstrictor response to NE (P < 0.02). Infusion of the alpha 1-agonist methoxamine raised blood pressure to the same extent, but did not change conducted vasoconstriction significantly. Blockade of endogenous ANG II by infusion of the AT1-receptor blocker losartan decreased conducted vasoconstriction to NE (P < 0.03). In parallel with the findings using NE, ANG II increased (P < 0.05) and losartan decreased (P < 0.01) conducted vasoconstriction when local electrical stimulation was used to initiate the conducted vascular response. CONCLUSION: The findings suggest that conducted vasoconstriction to NE and local electrical stimulation in rat mesenteric arterioles are modulated by ANG II, an increase in the plasma levels of ANG II increasing conducted vasoconstriction.
MESH: *Angiotensin-II-pharmacology; *Mesenteric-Arteries-drug-effects; *Norepinephrine-pharmacology; *Vasoconstrictor-Agents-pharmacology
MESH: Adrenergic-alpha-Agonists-pharmacology; Arterioles-drug-effects; Electric-Stimulation; Losartan-pharmacology; Methoxamine-pharmacology; Microscopy,-Video; Rats-; Rats,-Wistar; Receptors,-Angiotensin-drug-effects
TG: Animal; Male; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: pharmacology; drug-effects
RN: 0; 0; 0; 0; 11128-99-7; 114798-26-4; 390-28-3; 51-41-2
NM: Adrenergic-alpha-Agonists; Receptors,-Angiotensin; Vasoconstrictor-Agents; angiotensin-II-type-1-receptor; Angiotensin-II; Losartan; Methoxamine; Norepinephrine
SB: Index-Medicus
UD: 20001218
AN: 20082263
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 17 of 65 - MEDLINE (R) 1999 Part B
TI: Central role of the MAPK pathway in ang II-mediated DNA synthesis and migration in rat vascular smooth muscle cells.
AU: Xi,-X-P; Graf,-K; Goetze,-S; Fleck,-E; Hsueh,-W-A; Law,-R-E
AD: University of California at Los Angeles, School of Medicine, Division of Endocrinology, Diabetes, Los Angeles, CA, USA.
SO: Arterioscler-Thromb-Vasc-Biol. 1999 Jan; 19(1): 73-82
IS: 1079-5642
PY: 1999
LA: English
CP: UNITED-STATES
AB: Angiotensin II (Ang II) promotes vascular smooth muscle cell (VSMC) growth and migration, but the signaling pathways mediating these VSMC behaviors critical to restenosis and atherosclerosis are not completely known. The purpose of the present investigation was to define the role of mitogen-activated protein kinase (MAPK) in Ang II-induced DNA synthesis, migration, and c-fos induction in VSMCs. PD 98059, a synthetic inhibitor of MAPK kinase, or antisense oligodeoxynucleotides (ODNs) to deplete extracellular signal-regulated kinase (ERK)1 and ERK2 MAPKs, were used to inhibit MAPK signaling. PD 98059 at 30 micromol/L reduced Ang II-induced MAPK activity by 69% (P<0.01). Under these conditions, Ang II-induced DNA synthesis was completely inhibited (P<0.01), and Ang II-directed migration was attenuated by 76% (P<0.05). In contrast, induction of c-fos by Ang II was only partially suppressed (58% inhibition, P<0.01). Antisense ODNs against the initiation site of rat ERK1 and ERK2 MAPK mRNAs reduced corresponding protein levels by 63% (P<0.01) and completely inhibited MAPK activation by either Ang II (1 micromol/L) or 10% serum. Antisense ODNs (0.4 micromol/L) completely inhibited Ang II-induced DNA synthesis (P<0.01), decreased migration by 47% (P<0.01), and reduced c-fos induction by 40% (P<0.01 versus control ODN-transfected VSMCs). The Ang II type 1 (AT1)-receptor blocker irbesartan completely blocked DNA synthesis, migration, MAPK activation, and c-fos induction by Ang II in VSMCs. These results demonstrate that activation of MAPK plays a crucial role in Ang II-directed migration and DNA synthesis through the AT1 receptor. In contrast, Ang II-mediated c-fos induction and migration were only partially inhibited by either antisense ODNs or PD 98059, suggesting that other pathways in addition to the MAPK pathway may be involved in these actions of Ang II. We conclude that MAPK is a critical regulatory factor for Ang II-mediated migration and growth in VSMCs. Ang II-induced DNA synthesis showed a stronger MAPK dependence than did Ang II-directed migration or c-fos induction.
MESH: *Angiotensin-II-pharmacology; *Ca2+-Calmodulin-Dependent-Protein-Kinase-metabolism; *Cell-Movement-drug-effects; *DNA-biosynthesis; *Muscle,-Smooth,-Vascular-cytology; *Muscle,-Smooth,-Vascular-metabolism
MESH: Ca2+-Calmodulin-Dependent-Protein-Kinase-antagonists-and-inhibitors; Ca2+-Calmodulin-Dependent-Protein-Kinase-genetics; Enzyme-Activation; Enzyme-Inhibitors-pharmacology; Flavones-pharmacology; Oligodeoxyribonucleotides,-Antisense-pharmacology; Proto-Oncogene-Proteins-c-fos-biosynthesis; RNA,-Messenger-metabolism; Rats-; Rats,-Sprague-Dawley; Receptors,-Angiotensin-physiology; Signal-Transduction-drug-effects; p42-MAP-Kinase
TG: Animal; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: pharmacology; antagonists-and-inhibitors; genetics; metabolism; drug-effects; biosynthesis; cytology; physiology
RN: 0; 0; 0; 0; 0; 0; 0; 0; 11128-99-7; 9007-49-2; EC 2.7.10.-; EC 2.7.10.-; EC 2.7.10.-
NM: Enzyme-Inhibitors; Flavones; Oligodeoxyribonucleotides,-Antisense; PD-98059; Proto-Oncogene-Proteins-c-fos; RNA,-Messenger; Receptors,-Angiotensin; angiotensin-II-type-1-receptor; Angiotensin-II; DNA; Ca(2+)-Calmodulin-Dependent-Protein-Kinase; extracellular-signal-regulated-kinase-1; p42-MAP-Kinase
CN: RO1HL58328HLNHLBI
SB: Index-Medicus
UD: 20001218
AN: 99106025
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 18 of 65 - MEDLINE (R) 1999 Part B
TI: Molecular mechanisms of angiotensin II receptor internalization.
AU: Hunyady,-L
AD: Department of Physiology, Semmelweis University of Medicine, Budapest, Hungary. Hunyady@puskin.sote.hu
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S47-56
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: Angiotensin II (AngII) initiates cellular responses by activation of type I (AT1) and type 2 (AT2) angiotensin receptors. Both AT1 and AT1 receptors have seven transmembrane structures characteristic of G protein-coupled receptors, but only the AT1 receptor undergoes rapid internalization upon agonist binding. In addition to the agonist hormone, the peptide antagonist [Sar1,Ile8]AngII can also induce internalization of the AT1a receptor expressed in mammalian cell lines, but the nonpeptide AT1 receptor blocker losartan does not internalize. AT1 receptor internalization occurs via clathrin-coated pits, but there is evidence that, in contrast to the internalization of other G protein-coupled receptors, the internalization of the AT1 receptor is independent of dynamin and beta-arrestin. Mutagenesis studies demonstrated that AT1 receptor internalization requires two regions in the cytoplasmic tail of the receptor, but it is independent of G protein activation. The dependence of AT1 receptor internalization on the presence of a serine-threonine-rich region suggests that phosphorylation of the receptor tail may regulate the internalization process. The possible role of AT1 receptor internalization in sustained signal generation has been suggested, but its relationship to nuclear AngII receptors is not completely understood.
MESH: *Angiotensin-II-metabolism; *Receptors,-Angiotensin-metabolism
MESH: Amino-Acid-Sequence; Arrestin-metabolism; Cells,-Cultured; Clathrin-metabolism; Endocytosis-; GTP-Binding-Proteins-metabolism; Molecular-Sequence-Data; Phosphorylation-; Receptors,-Angiotensin-chemistry; Signal-Transduction
TG: Animal; Support,-Non-U.S.-Gov't
PT: Journal-Article; Review; Review,-Tutorial
SH: metabolism; chemistry
RN: 0; 0; 0; 0; 0; 11128-99-7; EC 3.6.1.-
NM: Arrestin; Clathrin; Receptors,-Angiotensin; angiotensin-II-type-1-receptor; angiotensin-II-type-2-receptor; Angiotensin-II; GTP-Binding-Proteins
SB: Index-Medicus
UD: 20001218
AN: 99107158
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 19 of 65 - MEDLINE (R) 1999 Part A
TI: Insulin resistance in adipocytes from spontaneously hypertensive rats: effect of long-term treatment with enalapril and losartan.
AU: Caldiz,-C-I; de-Cingolani,-G-E
AD: Center of Cardiovascular Research, School of Medicine, National University of La Plata, Argentina.
SO: Metabolism. 1999 Aug; 48(8): 1041-6
IS: 0026-0495
PY: 1999
LA: English
CP: UNITED-STATES
AB: Insulin responsiveness was studied in isolated adipocytes from the normotensive Wistar Kyoto (WKY) rat and the spontaneously hypertensive rat (SHR). The effect of insulin (0.1 to 5 nmol/L) on glucose uptake (glucose transport and lipogenesis) was measured, and the maximal effect of insulin (Emax) and the dose of insulin required to elicit 50% of the maximal response (EC50) were calculated. A diminished Emax on lipogenesis without changes in the EC50 was detected in SHRs. The Emax was 0.49 +/- 0.09 (SHR) and 1.16 +/- 0.14 (WKY) micromol/10(5) cells (P < .05), and the EC50 was 0.13 +/- 0.03 and 0.11 +/- 0.02 nmol/L for WKY and SHR, respectively. Similar results were obtained when measuring insulin-stimulated glucose transport. A 30-day long-term treatment with enalapril (20 mg/kg/d) normalized insulin responsiveness in adipocytes from SHRs. The effect of enalapril was suppressed when SHRs were pretreated with enalapril and 150 microg/kg/d of the bradykinin (BK) B2-receptor blocker Hoe 140. Pretreatment with losartan (40 mg/kg/d) did not improve insulin action in the SHR. Since these results were obtained with isolated cells in which glucose availability was not a function of blood flow, and the effect of insulin in the SHR was improved by pretreatment with an angiotensin-converting enzyme (ACE) inhibitor but not with the AT1-receptor blocker, it appears that the insulin resistance linked to the hypertension is not related to changes in blood flow.
MESH: *Adipocytes-metabolism; *Antihypertensive-Agents-pharmacology; *Enalapril-pharmacology; *Hypertension-metabolism; *Insulin-Resistance; *Losartan-pharmacology
MESH: Adipocytes-drug-effects; Antihypertensive-Agents-therapeutic-use; Biological-Transport; Enalapril-therapeutic-use; Glucose-metabolism; Hypertension-drug-therapy; Losartan-therapeutic-use; Rats-; Rats,-Inbred-SHR; Rats,-Inbred-WKY
TG: Animal; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: drug-effects; metabolism; pharmacology; therapeutic-use; drug-therapy
RN: 0; 114798-26-4; 50-99-7; 75847-73-3
NM: Antihypertensive-Agents; Losartan; Glucose; Enalapril
SB: Index-Medicus
UD: 20001218
AN: 99387327
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 20 of 65 - MEDLINE (R) 1999 Part A
TI: Valsartan/hydrochlorothiazide.
AU: Langtry,-H-D; McClellan,-K-J
AD: Adis International Limited, Auckland, New Zealand.
SO: Drugs. 1999 May; 57(5): 751-5; discussion 756-8
IS: 0012-6667
PY: 1999
LA: English
CP: NEW-ZEALAND
AB: Valsartan/hydrochlorothiazide (HCTZ) combines an angiotensin II AT1 receptor blocker with a thiazide diuretic to produce additive blood pressure reductions without major effects on heart rate. HCTZ did not significantly alter valsartan pharmacokinetics; during combination therapy, HCTZ pharmacokinetics differed from those seen with HCTZ monotherapy. In clinical trials in patients with essential hypertension, adding HCTZ 12.5 or 25 mg/day to valsartan 80 mg/day resulted in a greater blood pressure reduction than increasing the valsartan dosage from 80 to 160 mg/day. The valsartan/HCTZ combination was generally more effective than either drug given alone. Efficacy of the combination was maintained during up to 3 years of treatment. Valsartan/HCTZ was well tolerated in both short and long term trials. The most common adverse events were dizziness, headache and fatigue. The overall incidence of adverse events with the combination was similar to that with placebo. HCTZ-induced hypokalaemia was less common during combination therapy.
MESH: *Antihypertensive-Agents-pharmacology; *Hydrochlorothiazide-pharmacology; *Hypertension-drug-therapy; *Tetrazoles-pharmacology; *Valine-analogs-and-derivatives
MESH: Antihypertensive-Agents-pharmacokinetics; Clinical-Trials; Drug-Combinations; Heart-Rate-drug-effects; Hydrochlorothiazide-pharmacokinetics; Tetrazoles-pharmacokinetics; Valine-pharmacokinetics; Valine-pharmacology
TG: Human
PT: Journal-Article; Review; Review,-Tutorial
SH: pharmacokinetics; pharmacology; drug-effects; drug-therapy; analogs-and-derivatives
RN: 0; 0; 0; 137862-53-4; 58-93-5; 7004-03-7
NM: Antihypertensive-Agents; Drug-Combinations; Tetrazoles; valsartan; Hydrochlorothiazide; Valine
SB: Index-Medicus
UD: 20001218
AN: 99279740
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 21 of 65 - MEDLINE (R) 1999 Part A
TI: Losartan-sensitive renal damage caused by chronic NOS inhibition does not involve increased renal angiotensin II concentrations.
AU: Verhagen,-A-M; Braam,-B; Boer,-P; Grone,-H-J; Koomans,-H-A; Joles,-J-A
AD: Department of Nephrology, University Hospital Utrecht, The Netherlands.
SO: Kidney-Int. 1999 Jul; 56(1): 222-31
IS: 0085-2538
PY: 1999
LA: English
CP: UNITED-STATES
AB: BACKGROUND: Chronic nitric oxide synthase (NOS) inhibition results in hypertension, proteinuria, and renal morphological changes. Continuous angiotensin II (Ang II) blockade prevents these effects, suggesting an essential role of Ang II. However, it is not known whether renal Ang II concentrations are primarily increased or whether the scarcity of NO allows normal concentrations of Ang II to cause these detrimental effects. Therefore, we measured renal Ang II concentrations before and during the development of renal damage. METHODS: Group 1 served as controls. Groups 2 through 5 received the NOS inhibitor Nomega-nitro-L-arginine (L-NNA; 40 mg/kg/day) for 4, 7, 14, and 21 days, respectively. Systolic blood pressure (SBP), proteinuria, glomerular filtration rate (GFR), and renal and blood Ang II were measured. In a separate experiment, rats were treated with L-NNA + the Ang II AT1 receptor blocker losartan to determine the functional effects of endogenous Ang II during chronic NOS inhibition. RESULTS: L-NNA treatment resulted in an increase in SBP from day 4 (161 +/- 4 vs. 135 +/- 4 mm Hg in control, P < 0.05) to day 21 (230 +/- 9 mm Hg). GFR was decreased from day 4 (1.9 +/- 0.2 vs. 2.5 +/- 0.2 ml/min in control, P < 0.05) to day 21 (1.2 +/- 0.2 ml/min). Proteinuria was increased from day 14 (85 +/- 14 vs. 6 +/- 1 mg/day in control, P < 0.05) to day 21 (226 +/- 30 mg/day). L-NNA treatment during four days resulted in a significant decrease in renal Ang II (183 +/- 32 vs. 454 +/- 40 fmol/g in control, P < 0.05). On day 7, 14, and 21, renal Ang II was not significantly different from the control. Blood Ang II was not significantly different from the control on days 4, 7, and 14 but was significantly increased after 21 days of L-NNA treatment (215 +/- 35 vs. 78 +/- 13 fmol/ml in control, P < 0.05). Ang II type-1 (AT1) receptor blockade prevented the severe renal injury and hypertension induced by chronic NOS inhibition. CONCLUSIONS: Losartan-sensitive renal damage caused by chronic NOS inhibition does not involve increased renal Ang II concentrations. This suggests that the detrimental effects of endogenous Ang II are increased during chronic NOS inhibition. Thus, when NO levels are low, normal Ang II concentrations can cause renal injury and hypertension.
MESH: *Angiotensin-II-metabolism; *Kidney-drug-effects; *Kidney-pathology; *Losartan-pharmacology; *Nitric-Oxide-Synthase-antagonists-and-inhibitors; *Receptors,-Angiotensin-antagonists-and-inhibitors
MESH: Angiotensin-II-blood; Blood-Pressure-drug-effects; Enzyme-Inhibitors-pharmacology; Kidney-metabolism; Kidney-physiopathology; Nitroarginine-pharmacology; Osmolar-Concentration; Rats-; Rats,-Sprague-Dawley; Time-Factors
TG: Animal; Male; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: blood; metabolism; drug-effects; pharmacology; pathology; physiopathology; antagonists-and-inhibitors
RN: 0; 0; 0; 11128-99-7; 114798-26-4; 2149-70-4; EC 1.14.13.39
NM: Enzyme-Inhibitors; Receptors,-Angiotensin; angiotensin-II-type-1-receptor; Angiotensin-II; Losartan; Nitroarginine; Nitric-Oxide-Synthase
SB: Index-Medicus
UD: 20001218
AN: 99340510
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 22 of 65 - MEDLINE (R) 1999 Part A
TI: Brain renin-angiotensin system and sympathetic hyperactivity in rats after myocardial infarction.
AU: Zhang,-W; Huang,-B-S; Leenen,-F-H
AD: Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada K1Y 4W7.
SO: Am-J-Physiol. 1999 May; 276(5 Pt 2): H1608-15
IS: 0002-9513
PY: 1999
LA: English
CP: UNITED-STATES
AB: Blockade of brain "ouabain" prevents the sympathetic hyperactivity and impairment of baroreflex function in rats with congestive heart failure (CHF). Because brain "ouabain" may act by activating the brain renin-angiotensin system (RAS), the aim of the present study was to assess whether chronic treatment with the AT1-receptor blocker losartan given centrally normalizes the sympathetic hyperactivity and impairment of baroreflex function in Wistar rats with CHF postmyocardial infarction (MI). After left coronary artery ligation (2 or 6 wk), rats received either intracerebroventricular losartan (1 mg. kg-1. day-1, CHF-Los) or vehicle (CHF-Veh) by osmotic minipumps. To assess possible peripheral effects of intracerebroventricular losartan, one set of CHF rats received the same rate of losartan subcutaneously. Sham-operated rats served as control. After 2 wk of treatment, mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) at rest and in response to air-jet stress and intracerebroventricular injection of the alpha2-adrenoceptor-agonist guanabenz were measured in conscious animals. Arterial baroreflex function was evaluated by ramp changes in MAP. Compared with sham groups, CHF-Veh groups showed impaired arterial baroreflex control of HR and RSNA, increased sympathoexcitatory and pressor responses to air-jet stress, and increased sympathoinhibitory and hypotensive responses to guanabenz. The latter is consistent with decreased activity in sympathoinhibitory pathways. Chronic intracerebroventricular infusion of losartan largely normalized these abnormalities. In CHF rats, the same rate of infusion of losartan subcutaneously was ineffective. In sham-operated rats, losartan intracerebroventricularly or subcutaneously did not affect sympathetic activity. We conclude that the chronic increase in sympathoexcitation, decrease in sympathoinhibition, and desensitized baroreflex function in CHF all appear to depend on the brain RAS, since this whole pattern of changes can be normalized by chronic central AT1-receptor blockade with losartan.
MESH: *Brain-metabolism; *Myocardial-Infarction-physiopathology; *Renin-Angiotensin-System-physiology; *Sympathetic-Nervous-System-metabolism
MESH: Angiotensin-II-pharmacology; Antihypertensive-Agents-pharmacology; Baroreflex-drug-effects; Baroreflex-physiology; Blood-Pressure-drug-effects; Brain-blood-supply; Cardiotonic-Agents-pharmacology; Enzyme-Inhibitors-pharmacology; Guanabenz-pharmacology; Heart-Failure,-Congestive-physiopathology; Heart-Rate-drug-effects; Injections,-Intraventricular; Losartan-pharmacology; Nitroprusside-pharmacology; Ouabain-pharmacology; Phenylephrine-pharmacology; Rats-; Rats,-Wistar; Receptors,-Angiotensin-antagonists-and-inhibitors; Stress-physiopathology; Sympathetic-Nervous-System-blood-supply; Sympathetic-Nervous-System-chemistry
TG: Animal; Male; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: pharmacology; drug-effects; physiology; blood-supply; metabolism; physiopathology; antagonists-and-inhibitors; chemistry
RN: 0; 0; 0; 0; 0; 11128-99-7; 114798-26-4; 15078-28-1; 5051-62-7; 59-42-7; 630-60-4
NM: Antihypertensive-Agents; Cardiotonic-Agents; Enzyme-Inhibitors; Receptors,-Angiotensin; angiotensin-II-type-1-receptor; Angiotensin-II; Losartan; Nitroprusside; Guanabenz; Phenylephrine; Ouabain
SB: Index-Medicus
UD: 20001218
AN: 99261972
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 23 of 65 - MEDLINE (R) 1999 Part A
TI: Effects of AT1-receptor blockade on progression of left ventricular dysfunction in dogs with heart failure.
AU: Tanimura,-M; Sharov,-V-G; Shimoyama,-H; Mishima,-T; Levine,-T-B; Goldstein,-S; Sabbah,-H-N
AD: Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit 48202, Michigan, USA.
SO: Am-J-Physiol. 1999 Apr; 276(4 Pt 2): H1385-92
IS: 0002-9513
PY: 1999
LA: English
CP: UNITED-STATES
AB: The objective of the present study was to determine the effects of early long-term monotherapy with the angiotensin II AT1-receptor antagonist valsartan on the progression of left ventricular (LV) dysfunction and remodeling in dogs with moderate heart failure (HF). Studies were performed in 30 dogs with moderate HF produced by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LV ejection fraction was 30-40%. Two weeks after the last embolization, dogs were randomized to 3 mo of oral therapy with low-dose valsartan (400 mg twice daily, n = 10), to high-dose valsartan (800 mg twice daily, n = 10), or to no treatment at all (control, n = 10). Treatment with valsartan significantly reduced mean aortic pressure and LV end-diastolic pressure compared with control. In untreated dogs, LV ejection fraction decreased (37 +/- 1 vs. 29 +/- 1%, P = 0.001) and end-systolic volume (ESV) and end-diastolic volume (EDV) increased (81 +/- 5 vs. 92 +/- 5 ml, P < 0.001; 51 +/- 3 vs. 65 +/- 3 ml, P = 0.001, respectively) after 3 mo of follow-up compared with those levels before follow-up. In dogs treated for 3 mo with low-dose valsartan, ejection fraction was preserved (37 +/- 1 vs. 38 +/- 2%, pretreatment vs. posttreatment) as was ESV but not EDV. In dogs treated for 3 mo with high-dose valsartan, ejection fraction decreased (35 +/- 1 vs. 31 +/- 2%, P = 0.02) and ESV and EDV increased in a manner comparable to those levels in controls. Valsartan had no significant effects on cardiomyocyte hypertrophy or on the extent of interstitial fibrosis. We conclude that, for dogs with moderate HF, early long-term therapy with the AT1-receptor blocker valsartan decreases preload and afterload but has only limited benefits in attenuating the progression of LV dysfunction and chamber remodeling.
MESH: *Cardiac-Output,-Low-physiopathology; *Receptors,-Angiotensin-antagonists-and-inhibitors; *Ventricular-Dysfunction,-Left-physiopathology
MESH: Cardiac-Output,-Low-drug-therapy; Cardiac-Output,-Low-pathology; Disease-Progression; Dogs-; Dose-Response-Relationship,-Drug; Tetrazoles-therapeutic-use; Valine-analogs-and-derivatives; Valine-therapeutic-use; Ventricular-Dysfunction,-Left-drug-therapy; Ventricular-Dysfunction,-Left-pathology; Ventricular-Remodeling-drug-effects
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: drug-therapy; pathology; physiopathology; antagonists-and-inhibitors; therapeutic-use; analogs-and-derivatives; drug-effects
RN: 0; 0; 0; 137862-53-4; 7004-03-7
NM: Receptors,-Angiotensin; Tetrazoles; angiotensin-II-type-1-receptor; valsartan; Valine
CN: HL4909004HLNHLBI
SB: Index-Medicus
UD: 20001218
AN: 99216222
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 24 of 65 - MEDLINE (R) 1999 Part A
TI: Resetting of exaggerated tubuloglomerular feedback activity in acutely volume-expanded young SHR.
AU: Brannstrom,-K; Arendshorst,-W-J
AD: Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545, USA.
SO: Am-J-Physiol. 1999 Mar; 276(3 Pt 2): F409-16
IS: 0002-9513
PY: 1999
LA: English
CP: UNITED-STATES
AB: One purpose of the present study was to evaluate the ability of 7-wk-old spontaneously hypertensive rats (SHR) to reset tubuloglomerular feedback (TGF) activity in response to acute volume expansion (VE). Second, we evaluated the contribution of ANG II, via its action on AT1 receptors, to TGF control of glomerular function during VE. TGF was assessed by micropuncture methods and proximal tubular stop-flow pressure (SFP) determinations in SHR, Wistar-Kyoto rats (WKY), and Sprague-Dawley rats (SD). During euvolemia SHR exhibited enhanced TGF activity. In the same animals acute VE was achieved by infusion of saline (5 ml. h-1. 100 g body wt-1). VE led to resetting of TGF in all three strains. Maximal SFP responses, elicited by a 30-40 nl/min loop of Henle perfusion rate, decreased from 19 to 12 mmHg in SHR and, on average, from 11 to 5 mmHg in WKY and SD (P < 0.001). Tubular flow rate producing a half-maximal response (turning point) shifted to higher flow rates during VE, from 12 to 14 nl/min in SHR and from 15 to 19 nl/min in WKY. Administration of the AT1 receptor blocker candesartan (0.05 mg/kg iv) during sustained VE decreased TGF-mediated reductions in SFP in SHR and slightly increased the turning point in WKY. Nevertheless, other parameters of TGF activity were unaffected by AT1 receptor blockade. In conclusion, young SHR possess the ability to reset TGF activity in response to VE to a degree similar to compensatory adjustments in WKY. However, TGF remains enhanced in SHR during VE. ANG II and its action on AT1 receptors are in part responsible for the exaggerated SFP responses in young SHR during VE.
MESH: *Kidney-Glomerulus-physiology; *Kidney-Tubules-physiology; *Plasma-Substitutes-pharmacology; *Rats,-Inbred-SHR-physiology
MESH: Angiotensin-II-physiology; Benzimidazoles-pharmacology; Feedback-; Loop-of-Henle-physiology; Perfusion-; Pressure-; Punctures-; Rats-; Rats,-Inbred-WKY; Rats,-Sprague-Dawley; Receptors,-Angiotensin-antagonists-and-inhibitors; Receptors,-Angiotensin-physiology; Sodium-Chloride-pharmacology; Tetrazoles-pharmacology
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: physiology; pharmacology; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 0; 11128-99-7; 139481-59-7; 7647-14-5
NM: Benzimidazoles; Plasma-Substitutes; Receptors,-Angiotensin; Tetrazoles; angiotensin-II-type-1-receptor; Angiotensin-II; CV-11974; Sodium-Chloride
CN: HL02334HLNHLBI
SB: Index-Medicus
UD: 20001218
AN: 99170605
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 25 of 65 - MEDLINE (R) 1999 Part A
TI: AT1 calcium signaling in renal vascular smooth muscle cells.
AU: Iversen,-B-M; Arendshorst,-W-J
AD: Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, USA. Bjarne.Iversen@meda.uib.no
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S84-9
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: Experiments were conducted to gain insight into calcium signaling mechanisms triggered by angiotensin II (AngII) stimulation in vascular smooth muscle cells (SMC) freshly isolated from preglomerular vessels of normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Cytosolic calcium concentration ([Ca2+]i) was measured using ratiometric Fura-2 fluorescence and a microscope-based photometer. Vascular SMC from preglomerular vessels were isolated and dispersed using an iron oxide-sieving method combined with collagenase treatment. AngII produced rapid increases in [Ca2+]i that remained elevated for the duration of continued stimulation. The same pattern of time response was observed in WKY and in SHR. AngII elicited dose-dependent increases in [Ca2+]i in groups of individual preglomerular arteriolar SMC from both strains. AngII (10(-10) M) induced an increase from baseline levels in WKY and SHR (37+/-9 and 32+/-13 nM; P < 0.05). In response to 10(-6) M AngII, steady-state responses were 165+/-30 and 170+/-35 nM (P < 0.01). The responses did not differ between strains (P > 0.4). The effects of AngII were inhibited by 88% by the AT1 receptor blocker candesartan in renal SMC. In SMC pretreated with calcium-free medium, baseline [Ca2+]i fell by about 60 nM. Thereafter, AngII did not elicit any [Ca2+]i response either in WKY or in SHR when calcium entry was prevented. Also, after prestimulation by AngII, a calcium-free solution completely reversed the effects of AngII. This study shows that AngII acts through AT1 receptors to stimulate [Ca2+]i by a predominant action on calcium entry with no evidence for calcium mobilization. Other studies have demonstrated that calcium entry in these SMC is mediated by voltage-gated, L-type entry channels sensitive to dihydropyridine agents. No strain differences were noted between the actions of AngII on individual renal SMC from SHR and normotensive control animals.
MESH: *Calcium-Signaling; *Kidney-Glomerulus-blood-supply; *Muscle,-Smooth,-Vascular-metabolism; *Receptors,-Angiotensin-metabolism
MESH: Angiotensin-II-pharmacology; Benzimidazoles-pharmacology; Calcium-metabolism; Cells,-Cultured; Egtazic-Acid; Rats-; Rats,-Inbred-SHR; Rats,-Inbred-WKY; Receptors,-Angiotensin-antagonists-and-inhibitors; Tetrazoles-pharmacology
TG: Animal; Male
PT: Journal-Article
SH: pharmacology; metabolism; blood-supply; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 11128-99-7; 139481-59-7; 67-42-5; 7440-70-2
NM: Benzimidazoles; Receptors,-Angiotensin; Tetrazoles; angiotensin-II-type-1-receptor; Angiotensin-II; CV-11974; Egtazic-Acid; Calcium
SB: Index-Medicus
UD: 20001218
AN: 99107163
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 26 of 65 - MEDLINE (R) 1999 Part A
TI: Mesangial AT1 receptors: expression, signaling, and regulation.
AU: Ardaillou,-R; Chansel,-D; Chatziantoniou,-C; Dussaule,-J-C
AD: Institut National de la Sante et de la Recherche Medicale U 489, Hopital Tenon, Paris, France. raymond.ardaillou@tnn.ap-hop-paris.fr
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S40-6
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: Mesangial cells are one of the main targets of angiotensin II (AngII) in the renal cortex. AngII receptors on mesangial cells are of high affinity (nanomolar range). They belong to the AT1 subtype as shown by the inhibitory effect of AT1 antagonists on [125I]-Sar1, Ala8 AngII binding and on all of the biologic effects mediated by AngII, such as cytosolic calcium stimulation, inositol phosphate formation, prostaglandin production, and cell contraction. AngII also exerts long-term effects on mesangial cells, including stimulation of cell growth and synthesis of a variety of proteins, essentially the components of the extracellular matrix (collagen, fibronectin) and the type 1 inhibitor of plasminogen activator. These effects are mediated, at least in part, by autocrine products, in particular endothelin, platelet-derived growth factor, and transforming growth factor-beta, whose synthesis is enhanced by AngII. Treatment by an AT1 receptor blocker of mice with experimental nephritis inhibits activation of type I collagen alpha2 chain promoter and prevents the development of glomerulosclerosis. AngII receptors in rat mesangial cells are equally distributed between the AT1A and AT1B isoforms. Treatment of these cells by AngII or losartan, an AT1 receptor blocker, has no effect on AT1A and AT1B receptor mRNA expression, whereas candesartan, another AT1 receptor blocker, increases and dexamethasone decreases this expression.
MESH: *Angiotensin-II-pharmacology; *Glomerular-Mesangium-metabolism; *Receptors,-Angiotensin-biosynthesis
MESH: Benzimidazoles-pharmacology; Binding,-Competitive; Cells,-Cultured; Gene-Expression-Regulation; Losartan-pharmacology; Receptors,-Angiotensin-antagonists-and-inhibitors; Signal-Transduction; Tetrazoles-pharmacology
TG: Animal; Human
PT: Journal-Article; Review; Review,-Tutorial
SH: pharmacology; metabolism; antagonists-and-inhibitors; biosynthesis
RN: 0; 0; 0; 0; 11128-99-7; 114798-26-4; 139481-59-7
NM: Benzimidazoles; Receptors,-Angiotensin; Tetrazoles; angiotensin-II-type-1-receptor; Angiotensin-II; Losartan; CV-11974
SB: Index-Medicus
UD: 20001218
AN: 99107157
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 27 of 65 - MEDLINE (R) 1999 Part A
TI: Candesartan: a new-generation angiotensin II AT1 receptor blocker: pharmacology, antihypertensive efficacy, renal function, and renoprotection.
AU: Morsing,-P
AD: CV Pharmacology, Preclinical R&D, Astra Hassle AB, Molndal, Sweden. peter.morsing@hassle.se.astra.com
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S248-54
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: Candesartan, which is the active compound formed during adsorption of candesartan cilexetil, is one of the new generation of angiotensin II AT1 receptor blockers. Candesartan is an insurmountable blocker with a slow dissociation from the AT1 receptor, and it has been shown to effectively reduce BP in humans and in a variety of genetic and experimental models of hypertension. Possible mechanisms for a better effect in BP reduction compared with losartan may be the insurmountable characteristics of binding or more pronounced renal effects, but these need further evaluation. Candesartan has favorable effects on renal function demonstrated in both humans and animals, and has also been shown to protect the kidney in several models of renal injury. The beneficial effects exerted by candesartan could even be demonstrated in experimental models of hypertension in which BP is affected little, if at all. The renoprotective effects have been observed in the regulation of gene expression, as well as in biochemical and histologic evaluations.
MESH: *Antihypertensive-Agents-pharmacology; *Kidney-drug-effects; *Receptors,-Angiotensin-antagonists-and-inhibitors
MESH: Benzimidazoles-pharmacokinetics; Benzimidazoles-pharmacology; Biphenyl-Compounds-pharmacology; Disease-Models,-Animal; Hemodynamics-drug-effects; Hypertension-drug-therapy; Hypertension-physiopathology; Kidney-physiopathology; Losartan-pharmacology; Tetrazoles-pharmacokinetics; Tetrazoles-pharmacology
TG: Animal; Comparative-Study; Human
PT: Journal-Article; Review; Review,-Tutorial
SH: pharmacology; pharmacokinetics; drug-effects; drug-therapy; physiopathology; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 0; 0; 114798-26-4; 138402-11-6; 139481-59-7; 145040-37-5
NM: Antihypertensive-Agents; Benzimidazoles; Biphenyl-Compounds; Receptors,-Angiotensin; Tetrazoles; angiotensin-II-type-1-receptor; Losartan; irbesartan; CV-11974; TCV-116
SB: Index-Medicus
UD: 20001218
AN: 99107191
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 28 of 65 - MEDLINE (R) 1999 Part A
TI: Coinhibition of immune and renin-angiotensin systems reduces the pace of glomerulosclerosis in the rat remnant kidney.
AU: Hamar,-P; Peti-Peterdi,-J; Razga,-Z; Kovacs,-G; Heemann,-U; Rosivall,-L
AD: Department of Pathophysiology, International Nephrological Research and Training Center, Semmelweis University, Budapest, Hungary. hampet@net.sote.hu
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S234-8
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: The development of progressive glomerulosclerosis (GS) has been attributed to a number of humoral and hemodynamic factors, however, neither the exact pathomechanism nor the prevention and treatment have been clearly established. Renin-angiotensin system (RAS), interleukin-2 (IL-2)-activated T cells, systemic BP, and serum lipid levels all have been recognized as pathogenetic factors. According to our working hypothesis, a combination therapy with the inhibition of RAS and IL-2 system may be more potent in the prevention of the progression of GS than a monotherapy. After 5/6 subtotal nephrectomy, rats were treated with either the angiotensin-converting enzyme-blocker enalapril (E), the angiotensin II AT1 receptor blocker candesartan cilexetil (CA), the IL-2 synthesis inhibitor tacrolimus (T), or a combination of these agents. Proteinuria, as a functional hallmark of GS, was determined regularly, and at week 16, systolic BP, plasma total cholesterol, and triglyceride (TG) levels were measured and kidneys were harvested for morphologic and immunohistochemical analysis. Combination therapy was more effective (proteinuria: CA + T: 29.3+/-12.8 mg/24 h, E + T: 31.3+/-13.0 mg/24 h; GS: CA + T: 10.7+/-4.1%, E + T: 8.3+/-4.6%, P < 0.01) than monotherapy (proteinuria: T: 49.3+/-17.3 mg/24 h, CA: 53.2+/-18.1 mg/24 h, E: 51.1+/-26.6 mg/24 h; GS: T: 10.9+/-4.4%, CA: 23.8+/-4%, E: 14.2+/-5.3%, P < 0.05, with control values of proteinuria: 77.6+/-27.1 mg/24 h and GS: 28+/-2.9%). The number of infiltrating ED-1 (rat macrophage marker) macrophages (T: 161.5+/-51.2 cells/field of view, CA: 203.6+/-102.3, E: 178.6+/-35.3, CA + T: 140.2+/-63.2, E + T:128.2+/-75.6), and CD-5+ (rat T cell marker) T lymphocytes (CA + T: 261.5+/-103.6, E + T: 236+/-94.8) was significantly reduced by the treatment protocols (controls: ED-1: 356+/-100, CD-5: 482.9+/-154.5). These results indicate that an inhibition of RAS either with angiotensin-converting enzyme or AT1 receptor blockade, together with the inhibition of IL-2 synthesis, is more effective in the prevention of GS than a single treatment alone.
MESH: *Antihypertensive-Agents-therapeutic-use; *Glomerulosclerosis,-Focal-drug-therapy; *Immunosuppressive-Agents-therapeutic-use; *Kidney-drug-effects
MESH: Benzimidazoles-therapeutic-use; Blood-Pressure-drug-effects; Cholesterol-blood; Disease-Models,-Animal; Enalapril-therapeutic-use; Glomerulosclerosis,-Focal-blood; Glomerulosclerosis,-Focal-urine; Immune-System-drug-effects; Interleukin-2-biosynthesis; Kidney-immunology; Kidney-metabolism; Nephrectomy-; Proteinuria-urine; Rats-; Rats,-Wistar; Renin-Angiotensin-System-drug-effects; Tacrolimus-therapeutic-use; Tetrazoles-therapeutic-use; Triglycerides-blood
TG: Animal; Male; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: therapeutic-use; drug-effects; blood; drug-therapy; urine; biosynthesis; immunology; metabolism
RN: 0; 0; 0; 0; 0; 0; 109581-93-3; 139481-59-7; 57-88-5; 75847-73-3
NM: Antihypertensive-Agents; Benzimidazoles; Immunosuppressive-Agents; Interleukin-2; Tetrazoles; Triglycerides; Tacrolimus; CV-11974; Cholesterol; Enalapril
SB: Index-Medicus
UD: 20001218
AN: 99107188
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 29 of 65 - MEDLINE (R) 1999 Part A
TI: Angiotensin II stimulates macula densa basolateral sodium/hydrogen exchange via type 1 angiotensin II receptors.
AU: Bell,-P-D; Peti-Peterdi,-J
AD: Nephrology Research and Training Center, Department of Medicine, University of Alabama at Birmingham, 35294, USA. dbell@nrtc.dom.uab.edu
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S225-9
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: Angiotensin II (AngII) enhances tubuloglomerular feedback responses and is considered to be a specific modulator of feedback activity. The sites at which AngII interacts with the signal transmission process remain unknown. In certain renal epithelia, AngII stimulates Na/H exchange activities. Evidence for the regulation of macula densa apical Na/H exchange by AngII was recently reported. Because macula densa cells also express a basolateral Na/H exchanger, the possibility that AngII stimulates this exchanger activity was investigated. In preparations of isolated perfused thick ascending limb with attached glomerulus dissected from rabbit kidney, the intracellular pH (pHi) of macula densa cells was measured with fluorescence microscopy using 2',7'-bis(2-carboxyethyl)-5-(and -6)carboxyfluorescein. Perfusion and bathing solutions were iso-osmotic Cl-free Ringer's solutions modified using N-methyl-D-glucamine and cyclamate as the Na and Cl substitutes, respectively. Control pHi, during perfusion with 0 mM Na and 150 mM Na in the bath, averaged 7.21+/-0.07 (n=10). Removal of Na from the bath (i.e., basolateral solution) decreased pHi by 0.39+/-0.06 units (n=5, P < 0.01). Addition of 10(-9) M AngII to the bath resulted in a significant increase in the Na-dependent acid load. This increase in Na-dependent cell acidification was completely blocked by coadministration of the AngII type 1 (AT1) receptor blocker candesartan (10(-8) M). In addition, AngII increased the rate of pHi recovery from the acid load induced by readdition of bath Na. This stimulatory effect of AngII was also completely reversed by coadministration of the AT1 receptor blocker candesartan. These results indicate that AngII stimulates macula densa basolateral Na/H exchange via AT1 receptors and therefore may affect tubuloglomerular feedback signal transmission, at least in part, through direct effects on macula densa transport processes.
MESH: *Angiotensin-II-pharmacology; *Kidney-Glomerulus-drug-effects; *Receptors,-Angiotensin-drug-effects; *Sodium-Hydrogen-Antiporter-metabolism
MESH: Benzimidazoles-pharmacology; Hydrogen-Ion-Concentration; Kidney-Glomerulus-metabolism; Rabbits-; Receptors,-Angiotensin-antagonists-and-inhibitors; Signal-Transduction-drug-effects; Sodium-Hydrogen-Antiporter-biosynthesis; Tetrazoles-pharmacology
TG: Animal; In-Vitro; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: pharmacology; drug-effects; metabolism; antagonists-and-inhibitors; biosynthesis
RN: 0; 0; 0; 0; 0; 11128-99-7; 139481-59-7
NM: Benzimidazoles; Receptors,-Angiotensin; Sodium-Hydrogen-Antiporter; Tetrazoles; angiotensin-II-type-1-receptor; Angiotensin-II; CV-11974
CN: NIDDK32032DKNIDDK
SB: Index-Medicus
UD: 20001218
AN: 99107186
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 30 of 65 - MEDLINE (R) 1999 Part A
TI: Effects of candesartan on angiotensin II-induced renal vasoconstriction in rats and mice.
AU: Ruan,-X; Purdy,-K-E; Oliverio,-M-I; Coffman,-T-M; Arendshorst,-W-J
AD: University of North Carolina at Chapel Hill, 27599-7545, USA.
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S202-7
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: This study determined the inhibitory effect of the angiotensin II (AngII) type I (AT1) receptor blocker candesartan on renal vascular reactivity in vivo. Reactivity to AngII before and during candesartan administration was assessed by measuring (by electromagnetic or ultrasonic flowmetry) renal blood flow responses to AngII in rats and mice. AngII produced greater renal vasoconstriction in 7-wk-old, spontaneously hypertensive rats than in Wistar-Kyoto rats. After indomethacin treatment, AngII (2 ng) produced 40% reductions in renal blood flow in both rat strains, without affecting systemic arterial pressure. Coadministration of candesartan blocked AngII effects in a dose-dependent manner, with similar levels of inhibition in spontaneously hypertensive rats and Wistar-Kyoto rats; maximal inhibition was 80%. In rats that had been pretreated (for 30 min) with intravenous candesartan, AngII-induced renal vasoconstriction was inhibited dose dependently up to 98%. To evaluate receptor subtype mediation, responses were compared in mice with or without the AT1A receptor (deleted by gene targeting). Intrarenal AngII (1 ng) caused a 32% reduction of renal blood flow in wild-type mice and an 8% reduction of renal blood flow in AT1A receptor-knockout mice. Ten nanograms of AngII were required to elicit 20% renal vasoconstriction in these mutant mice. Concurrent injection of candesartan caused dose-dependent inhibition of AngII up to 80%. The candesartan IC50 values for percentage changes in renal blood flow did not differ in the two groups of mice. These studies establish that candesartan is an effective, highly selective, AT1 receptor blocker, inhibiting renal vasoconstriction in rodents in a concentration- and time-dependent manner. Candesartan effectively blocks AT1A and AT1B receptors in renal resistance vessels of rodents, with similar efficacies in rats and mice.
MESH: *Angiotensin-II-antagonists-and-inhibitors; *Benzimidazoles-pharmacology; *Kidney-drug-effects; *Receptors,-Angiotensin-antagonists-and-inhibitors; *Tetrazoles-pharmacology
MESH: Angiotensin-II-administration-and-dosage; Benzimidazoles-therapeutic-use; Dose-Response-Relationship,-Drug; Hypertension-drug-therapy; Hypertension-genetics; Kidney-blood-supply; Mice-; Mice,-Knockout; Rats-; Rats,-Inbred-SHR; Rats,-Inbred-WKY; Receptors,-Angiotensin-genetics; Regional-Blood-Flow-drug-effects; Renal-Artery; Tetrazoles-therapeutic-use; Time-Factors; Vasoconstriction-drug-effects
TG: Animal; Comparative-Study; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: administration-and-dosage; antagonists-and-inhibitors; pharmacology; therapeutic-use; drug-therapy; genetics; blood-supply; drug-effects
RN: 0; 0; 0; 0; 11128-99-7; 139481-59-7
NM: Benzimidazoles; Receptors,-Angiotensin; Tetrazoles; angiotensin-II-type-1-receptor; Angiotensin-II; CV-11974
CN: HL02334HLNHLBI
SB: Index-Medicus
UD: 20001218
AN: 99107182
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 31 of 65 - MEDLINE (R) 1999 Part A
TI: Renal responses of the nonclipped kidney of two-kidney/one-clip Goldblatt hypertensive rats to type 1 angiotensin II receptor blockade with candesartan.
AU: Cervenka,-L; Navar,-L-G
AD: Tulane University School of Medicine, Department of Physiology, New Orleans, Louisiana 70112, USA.
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S197-201
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: Recent studies with normal rats indicated that systemic administration of the angiotensin II (AngII) type 1 (AT1) receptor blocker candesartan elicited divergent renal hemodynamic and excretory responses depending on the magnitude of associated decreases in mean arterial pressure. To evaluate the responses to candesartan in hypertensive rats, experiments were performed 25 d after unilateral renal arterial constriction with a 0.25-mm clip. The rats were anesthetized and prepared for acute clearance experiments. Control arterial pressure responses to a bolus AngII dose (50 ng) averaged 35+/-7 mmHg; the control decreases in cortical renal blood flow (RBF), measured with laser Doppler flowmetry, were 58+/-9%. The vasoconstrictor responses to AngII were abolished by candesartan doses of 1 and 0.1 mg/kg. Treatment with 0.01 mg/kg candesartan attenuated the arterial pressure responses but did not prevent the cortical RBF decreases. The highest dose of candesartan (1 mg/kg) elicited rapid reductions in arterial pressure (from 154+/-5 to 122+/-9 mmHg), leading to associated decreases in RBF (from 5.5+/-0.2 to 4.6+/-0.4 ml/min x g) and sodium excretion (from 0.4+/-0.1 to 0.2+/-0.1 microEq/min x g). The 0.1 mg/kg dose of candesartan led to gradual reductions in arterial pressure (from 155+/-5 to 140+/-5 mmHg), and there were significant increases in RBF (from 5.4+/-0.2 to 6.8+/-0.4 ml/min x g) and decreases in renal vascular resistance. However, this dose still decreased urine flow and sodium excretion. In contrast, when candesartan was administered at 0.01 mg/kg, a dose that did not significantly decrease arterial pressure, there were significant increases in RBF (26+/-11%) and urine flow (43+/-19%) and proportionately greater increases in sodium excretion (284+/-89%) and fractional sodium excretion (351+/-99%). These data demonstrate the divergent renal hemodynamic and sodium excretory responses to AT1 receptor blockade in hypertensive rats, depending on the magnitude of decreases in arterial pressure. The lower candesartan dose, which did not cause hypotension, elicited substantial increases in RBF and proportionally much greater increases in sodium excretion, revealing the direct renal vasodilation and natriuretic effects of AT1 receptor blockade.
MESH: *Benzimidazoles-therapeutic-use; *Hypertension,-Renal-drug-therapy; *Kidney-drug-effects; *Receptors,-Angiotensin-antagonists-and-inhibitors; *Tetrazoles-therapeutic-use
MESH: Angiotensin-II-pharmacology; Blood-Pressure-drug-effects; Dose-Response-Relationship,-Drug; Glomerular-Filtration-Rate; Hypertension,-Renal-urine; Rats-; Rats,-Sprague-Dawley; Regional-Blood-Flow-drug-effects; Sodium-urine; Time-Factors; Vasodilation-
TG: Animal; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: pharmacology; therapeutic-use; drug-effects; drug-therapy; urine; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 11128-99-7; 139481-59-7; 7440-23-5
NM: Benzimidazoles; Receptors,-Angiotensin; Tetrazoles; angiotensin-II-type-1-receptor; Angiotensin-II; CV-11974; Sodium
CN: HL26371HLNHLBI
SB: Index-Medicus
UD: 20001218
AN: 99107181
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 32 of 65 - MEDLINE (R) 1999 Part A
TI: Renin-angiotensin system dependence of renal hemodynamics in mice.
AU: Traynor,-T-R; Schnermann,-J
AD: Department of Physiology, The University of Michigan, Ann Arbor, USA.
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S184-8
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: Renin secretion from isolated, perfused, thick ascending limb/glomerulus preparations from mice, under baseline conditions, has been found to be approximately 10-fold higher than that observed with the same preparations from rabbits. Higher renin secretion rates appear to be accompanied by higher plasma renin activities in mice, compared with rats, rabbits, or humans. Experiments were performed to determine the extent of the renin-angiotensin system dependence of renal hemodynamics in mice. Administration of the type 1 angiotensin II (AT1) receptor blocker candesartan (10 mg/kg) to untreated control mice increased renal blood flow by 55% (from 1.8+/-0.2 to 2.8+/-0.2 ml/min) and decreased renal vascular resistance by 42% (from 55+/-7.5 to 31.8+/-2.3 mmHg x min/ml). Similarly, acute extracellular volume expansion increased renal blood flow by 84% and reduced renal vascular resistance by 48%. In mice with null mutations in either the AT1 receptor or the angiotensin-converting enzyme gene, renal vascular resistance was significantly lower than in wild-type mice. Tubuloglomerular feedback, which is an angiotensin II-dependent vasoconstrictor response, was found to be abolished in both strains of knockout mice. Acute AT1 receptor blockade by candesartan reduced tubuloglomerular feedback responses to a flow rate step change of 0 to 30 nl/min by approximately 80% (from 6.1+/-1.4 to 1.3+/-0.4 mmHg). Candesartan increased the steady-state autoregulatory index from 0.19 to 0.55 (in a pressure interval of 90 to 100 mmHg), suggesting reduced efficiency of steady-state autoregulation. These results indicate that the renin-angiotensin system exerts tonic control over renal vascular resistance in mice to a greater extent than previously observed in other mammalian species.
MESH: *Benzimidazoles-pharmacology; *Hemodynamics-physiology; *Kidney-Glomerulus-physiology; *Receptors,-Angiotensin-antagonists-and-inhibitors; *Renin-Angiotensin-System-physiology; *Tetrazoles-pharmacology
MESH: Glomerular-Filtration-Rate-drug-effects; Hemodynamics-drug-effects; Homeostasis-drug-effects; Kidney-Glomerulus-drug-effects; Mice-; Mice,-Knockout; Mutation-; Peptidyl-Dipeptidase-A-genetics; Receptors,-Angiotensin-genetics; Renin-analysis; Renin-secretion; Renin-Angiotensin-System-drug-effects; Vascular-Resistance-drug-effects
TG: Animal; Comparative-Study; In-Vitro; Male; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: pharmacology; drug-effects; physiology; genetics; antagonists-and-inhibitors; analysis; secretion
RN: 0; 0; 0; 0; 139481-59-7; EC 3.4.15.1; EC 3.4.23.15
NM: Benzimidazoles; Receptors,-Angiotensin; Tetrazoles; angiotensin-II-type-1-receptor; CV-11974; Peptidyl-Dipeptidase-A; Renin
CN: DK09489DKNIDDK; DK37448DKNIDDK; DK40042DKNIDDK
SB: Index-Medicus
UD: 20001218
AN: 99107179
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 33 of 65 - MEDLINE (R) 1999 Part A
TI: Candesartan cilexetil protects against loss of autoregulatory efficiency in angiotensin II-infused rats.
AU: Inscho,-E-W; Imig,-J-D; Deichmann,-P-C; Cook,-A-K
AD: Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. einscho@mailhost.tcs.tulane.edu
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S178-83
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: Renal autoregulatory efficiency is compromised in angiotensin-II (AngII)-dependent Goldblatt hypertension. The current studies were performed to assess renal autoregulatory capability in AngII-infused hypertensive rats and to determine the effect of chronic candesartan cilexetil treatment on autoregulatory behavior. Rats received chronic infusion of AngII (60 ng/min) or vehicle via an osmotic minipump implanted subcutaneously in the dorsum of the neck. Selected rats received the novel AT1 receptor blocker candesartan cilexetil (1.0 mg/kg per d) in the drinking water. Systolic BP averaged 118+/-1 mmHg (n=34) before pump implantation. Chronic AngII infusion for 6 d increased arterial pressure to 151+/-4 mmHg. Candesartan cilexetil administration prevented the AngII-dependent increase in systolic BP. Microvascular autoregulation experiments were performed in vitro using the blood-perfused juxtamedullary nephron technique combined with videomicroscopy. Renal perfusion pressure was set at 100 mmHg during the control period before being decreased to 65 mmHg. Afferent arteriolar diameter was measured continuously as the perfusion pressure was increased from 65 mmHg to 170 mmHg in 15-mmHg increments. Afferent arteriolar diameter in sham-treated rats was 120% of control at a perfusion pressure of 65 mmHg and decreased to 76% of the control diameter at 170 mmHg (n=6). This behavior is consistent with normal autoregulatory behavior. Arterioles from rats receiving chronic infusion of AngII exhibited compromised renal microvascular autoregulatory efficiency. Afferent arteriolar diameter in AngII-treated kidneys varied from 103 to 100% (n=6) of the control diameter over the same pressure range of 65 to 170 mmHg. This blunting of autoregulatory behavior was prevented by AT1 receptor blockade. In animals receiving AngII + candesartan cilexetil, stepwise changes in perfusion pressure elicited changes in afferent arteriolar diameter between 120 and 84% after 6 d of treatment (n=6). These data suggest that chronic elevations in circulating AngII and/or the associated increase in arterial pressure impairs renal autoregulatory capability. Furthermore, inhibition of AT1 receptors with candesartan cilexetil provides protection against AngII-mediated increases in arterial pressure and prevents the associated deterioration of renal autoregulatory responsiveness.
MESH: *Benzimidazoles-therapeutic-use; *Biphenyl-Compounds-therapeutic-use; *Hypertension-drug-therapy; *Kidney-drug-effects; *Receptors,-Angiotensin-antagonists-and-inhibitors
MESH: Angiotensin-II; Blood-Pressure-drug-effects; Homeostasis-drug-effects; Hypertension-chemically-induced; Hypertension-urine; Kidney-blood-supply; Kidney-physiology; Rats-; Rats,-Sprague-Dawley; Vasoconstriction-
TG: Animal; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: therapeutic-use; drug-effects; chemically-induced; drug-therapy; urine; blood-supply; physiology; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 11128-99-7; 145040-37-5
NM: Benzimidazoles; Biphenyl-Compounds; Receptors,-Angiotensin; angiotensin-II-type-1-receptor; Angiotensin-II; TCV-116
CN: DK44628DKNIDDK
SB: Index-Medicus
UD: 20001218
AN: 99107178
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 34 of 65 - MEDLINE (R) 1999 Part A
TI: Effects of candesartan on the renin system in conscious rats.
AU: Wagner,-C; Kurtz,-A
AD: Institut fur Physiologie der Universitat Regensburg, Germany.
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S169-71
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: This study aimed to assess and to compare the effects of cadesartan cilexetil on the renin system in rats. Male Sprague Dawley rats were orally treated either with the angiotensin-converting enzyme inhibitor ramipril (7.5 mg/kg per d), with the established AngII-AT1 receptor blocker losartan (40 mg/kg per d), or with candesartan cilexetil (1 mg/kg per d) for 3 d, and the effects of these treatments on plasma renin activity, renal renin mRNA levels, and adrenal levels of AngII-AT1a and AngII-AT1b receptor mRNA were determined. It was found that all drugs led to very similar increases in plasma renin activity and renin mRNA levels and to rather similar decreases in adrenal AngII-AT1b receptor mRNA levels. It is concluded therefore that the effects of candesartan on the renin system in vivo are not different from those obtained with angiotensin-converting enzyme inhibition or with the AngII-AT1 receptor blocker losartan.
MESH: *Benzimidazoles-pharmacology; *Biphenyl-Compounds-pharmacology; *Renin-blood; *Renin-Angiotensin-System-drug-effects
MESH: Adrenal-Glands-drug-effects; Adrenal-Glands-metabolism; Angiotensin-Converting-Enzyme-Inhibitors-pharmacology; Losartan-pharmacology; RNA,-Messenger-biosynthesis; Ramipril-pharmacology; Rats-; Rats,-Sprague-Dawley; Receptors,-Angiotensin-biosynthesis
TG: Animal; Comparative-Study; Male
PT: Journal-Article
SH: drug-effects; metabolism; pharmacology; biosynthesis; blood
RN: 0; 0; 0; 0; 0; 0; 0; 114798-26-4; 145040-37-5; 87333-19-5; EC 3.4.23.15
NM: Angiotensin-Converting-Enzyme-Inhibitors; Benzimidazoles; Biphenyl-Compounds; RNA,-Messenger; Receptors,-Angiotensin; angiotensin-II-type-1-receptor; angiotensin-II-type-2-receptor; Losartan; TCV-116; Ramipril; Renin
SB: Index-Medicus
UD: 20001218
AN: 99107176
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 35 of 65 - MEDLINE (R) 1999 Part A
TI: The effects of candesartan on human AT1 receptor-expressing Chinese hamster ovary cells.
AU: Vauquelin,-G; Fierens,-F-L; De-Backer,-J-P; Vanderheyden,-P-M
AD: Department of Molecular and Biochemical Pharmacology, Institute of Molecular Biology, Free University of Brussels (VUB), Sint-Genesius Rode, Belgium. gvauquel@vub.ac.be
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S15-7
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: Chinese hamster ovary cells expressing the cloned human angiotensin II receptor of the AT1 subtype (CHO-AT1 cells) were used as an 'in vitro" model system to investigate the action mechanism of the nonpeptide AT1 receptor blocker candesartan. In the presence of 10 mM LiCl, angiotensin II causes a long-lasting increase in the production of inositol phosphates in these cells. This effect is dose-dependent with half-maximal stimulation (EC50) at 3 nM angiotensin II. Pre-incubation of the cells for 30 min at 37 degrees C with candesartan decreases the maximal response to angiotensin II by up to 90%, with a half-maximal decrease at 0.5 nM candesartan. At this concentration, candesartan only produces a slight rightward shift of the angiotensin II dose-response curve. Recovery experiments on CHO-AT1 cells reveal that the inhibitory effect of candesartan is only slowly reversed after removal of the blocker. The insurmountable effect of candesartan can therefore be ascribed to its long-lasting inhibition of the AT1 receptor.
MESH: *Antihypertensive-Agents-pharmacology; *Benzimidazoles-pharmacology; *CHO-Cells-drug-effects; *Receptors,-Angiotensin-biosynthesis; *Tetrazoles-pharmacology
MESH: Angiotensin-II-antagonists-and-inhibitors; Angiotensin-II-pharmacology; CHO-Cells-metabolism; Dose-Response-Relationship,-Drug; Hamsters-; Inositol-Phosphates-biosynthesis; Lithium-Chloride; Receptors,-Angiotensin-genetics; Transfection-
TG: Animal; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: antagonists-and-inhibitors; pharmacology; drug-effects; metabolism; biosynthesis; genetics
RN: 0; 0; 0; 0; 0; 0; 11128-99-7; 139481-59-7; 7447-41-8
NM: Antihypertensive-Agents; Benzimidazoles; Inositol-Phosphates; Receptors,-Angiotensin; Tetrazoles; angiotensin-II-type-1-receptor; Angiotensin-II; CV-11974; Lithium-Chloride
SB: Index-Medicus
UD: 20001218
AN: 99107153
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 36 of 65 - MEDLINE (R) 1999 Part A
TI: Effects of the angiotensin AT1 receptor blocker candesartan on myocardial ischemic/reperfusion injury.
AU: Shimizu,-M; Sjoquist,-P-O; Wang,-Q-D; Ryden,-L
AD: Department of Cardiology, Karolinska Hospital, Stockholm, Sweden.
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S137-42
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: The effect of the insurmountable angiotensin II AT1 receptor blocker candesartan on ischemic/reperfusion injury was investigated in isolated rat hearts and in anesthetized pigs. The possible additive effect of candesartan on the cardioprotection by a calcium antagonist and a lipid peroxidation inhibitor was also studied. In Langendorff-perfused rat hearts, candesartan, in a dose-related manner, improved left ventricular functional recovery and reduced the no-reflow area following global ischemia and reperfusion. A similar degree of cardioprotection by candesartan (10 nM) and an equipotent concentration of another AT1 receptor blocker losartan (3 microM) was observed when ischemia was begun immediately after drug pretreatment. When a washout period was implemented between pretreatment and ischemia, the protective effect of candesartan, but not that of losartan, remained, suggesting that candesartan may provide a more efficient cardioprotection than losartan. In anesthetized pigs subjected to 45 min of coronary artery occlusion followed by 240 min of reperfusion, local coronary venous retroinfusion (0.042, 0.42, and 4.2 microM) of candesartan starting just before reperfusion improved, in a dose-related manner, the recovery of myocardial segment shortening (sonomicrometer) and reduced infarct size without persistent effect on regional myocardial blood flow (microspheres). A combination of candesartan, felodipine, and the lipid peroxidation inhibitor H290/51 produced a more pronounced infarct limitation than each of these agents alone. In conclusion, candesartan exerts a cardioprotective effect, via a local mechanism within the ischemic myocardium. A combination of drugs with different pharmacologic profiles may provide a better cardioprotection in the setting of myocardial ischemic/reperfusion compared with each individual compound.
MESH: *Benzimidazoles-therapeutic-use; *Myocardial-Ischemia-drug-therapy; *Myocardial-Reperfusion-Injury-drug-therapy; *Receptors,-Angiotensin-antagonists-and-inhibitors; *Tetrazoles-therapeutic-use
MESH: Antioxidants-therapeutic-use; Calcium-Channel-Blockers-therapeutic-use; Drug-Therapy,-Combination; Felodipine-therapeutic-use; Hemodynamics-drug-effects; Indoles-therapeutic-use; Losartan-therapeutic-use; Myocardial-Ischemia-pathology; Rats-; Rats,-Sprague-Dawley; Swine-
TG: Animal; Comparative-Study; Female; In-Vitro; Male; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: therapeutic-use; drug-effects; drug-therapy; pathology; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 0; 0; 0; 0; 114798-26-4; 139481-59-7; 72509-76-3
NM: Antioxidants; Benzimidazoles; Calcium-Channel-Blockers; H290-51; Indoles; Receptors,-Angiotensin; Tetrazoles; angiotensin-II-type-1-receptor; Losartan; CV-11974; Felodipine
SB: Index-Medicus
UD: 20001218
AN: 99107172
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 37 of 65 - MEDLINE (R) 1999 Part A
TI: Normalizing the expression of nitric oxide synthase by low-dose AT1 receptor antagonism parallels improved vascular morphology in hypertensive rats.
AU: Bennai,-F; Morsing,-P; Paliege,-A; Ketteler,-M; Mayer,-B; Tapp,-R; Bachmann,-S
AD: Institut fur Anatomie, Charite, Humboldt Universitat, Berlin, Germany.
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S104-15
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: In essential hypertension, stroke and kidney damage may result from an impaired interaction of vasoregulatory systems. Stroke-prone spontaneously hypertensive rats (SHRSP) were studied to analyze the effects of a low-dose treatment of the angiotensin II type 1 receptor (AT1) blocker candesartan cilexetil on the expression of nitric oxide synthases (NOS) and on vascular structure. Both treated and untreated SHRSP were kept on a stroke-promoting dietary regimen, and compared with Wistar Kyoto rats (WKY). Early mortality of untreated SHRSP was prevented by the treatment. In untreated SHRSP, cerebral intraparenchymal vessels of the parietal lobe showed lesions of the vascular wall and its periphery, such as proteinaceous deposits, perivascular dilated spaces, increase in phagocytic cells, and decreased actin immunostaining. Renal lesions were more pronounced comprising arteriolar occlusion, extensive loss of actin, increased alpha1(IV) collagen expression, and glomerular sclerotic as well as tubulointerstitial lesions. Beneficial effects of the AT1 blockade were more pronounced in brain than in kidney. Activity profile of NOS showed increased NADPH diaphorase staining in media and endothelium of SHRSP; endothelial NOS3 immunoreactivity was decreased, but instead, inducible NOS2 increased in untreated SHRSP. These changes were largely prevented in the treated group. NOS activity in macula densa cells was unchanged, whereas afferent arteriolar renin levels were increased in untreated SHRSP. Results demonstrate an effective reduction of hypertensive vascular changes with a nonpressor dose of candesartan. A "role switch" of vascular NOS in hypertension from physiologic NOS3 toward deleterious NOS2 is suggested, and its prevention by the AT1 blocker points to an angiotensin II-dependent, nitric oxide-mediated pathway that may impair endothelial function and aggravate defects of the blood-brain barrier and kidney structures.
MESH: *Benzimidazoles-pharmacology; *Brain-drug-effects; *Kidney-drug-effects; *Microcirculation-drug-effects; *Nitric-Oxide-Synthase-biosynthesis; *Receptors,-Angiotensin-antagonists-and-inhibitors; *Tetrazoles-pharmacology
MESH: Arterioles-drug-effects; Arterioles-enzymology; Arterioles-ultrastructure; Benzimidazoles-therapeutic-use; Blood-Pressure; Body-Weight; Brain-blood-supply; Brain-enzymology; Cerebrovascular-Disorders-etiology; Hypertension-drug-therapy; Kidney-blood-supply; Kidney-enzymology; Microcirculation-enzymology; Microcirculation-ultrastructure; NADPH-Dehydrogenase; Nitric-Oxide-Synthase-analysis; Rats-; Rats,-Inbred-SHR; Rats,-Inbred-WKY; Sodium,-Dietary; Tetrazoles-therapeutic-use
TG: Animal; Comparative-Study; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: drug-effects; enzymology; ultrastructure; pharmacology; therapeutic-use; blood-supply; etiology; drug-therapy; analysis; biosynthesis; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 0; 139481-59-7; EC 1.14.13.-; EC 1.14.13.-; EC 1.14.13.39; EC 1.6.99.1
NM: Benzimidazoles; Receptors,-Angiotensin; Sodium,-Dietary; Tetrazoles; angiotensin-II-type-1-receptor; CV-11974; endothelial-constitutive-nitric-oxide-synthase; inducible-nitric-oxide-synthase; Nitric-Oxide-Synthase; NADPH-Dehydrogenase
SB: Index-Medicus
UD: 20001218
AN: 99107168
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 38 of 65 - MEDLINE (R) 1999 Part A
TI: Analysis of the effects of candesartan on responses to angiotensin II in the hindquarters vascular bed of the cat.
AU: Champion,-H-C; Bivalacqua,-T-J; Lambert,-D-G; McNamara,-D-B; Kadowitz,-P-J
AD: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA. champion@mailhost.tcs.tulane.edu
SO: J-Am-Soc-Nephrol. 1999 Jan; 10 Suppl 11S101-3
IS: 1046-6673
PY: 1999
LA: English
CP: UNITED-STATES
AB: The effects of the nonpeptide angiotensin II (AngII) AT1 receptor blocker candesartan on responses to AngII were investigated in the hindquarters vascular bed of the cat. Under constant-flow conditions, injections of AngII into the hindquarters perfusion circuit elicited dose-dependent increases in perfusion pressure. Candesartan in a dose of 3 microg/kg intravenously (i.v.) decreased vasoconstrictor responses to AngII in a surmountable manner. At doses of 30 and 300 microg/kg i.v., candesartan shifted the dose-response curve to AngII to the right in an insurmountable manner, indicating an insurmountable blockade of AT1 receptors. The inhibitory effects of the larger doses of candesartan on responses to AngII were long in duration, and the AT1 receptor blocker had little effect on baseline pressures. Candesartan was without effect on vasoconstrictor responses to norepinephrine, U46619, PGF2alpha, vasopressin, BAY K8644; biphasic responses to endothelin-1; or on vasodilator responses to acetylcholine, albuterol, or levcromakalim. These results indicate that candesartan is a potent and selective angiotensin AT1 receptor blocker that can induce both surmountable and insurmountable AT1 receptor blockade and provide support for the hypothesis that there are "spare" AT1 receptors in the hindquarters vascular bed of the cat.
MESH: *Angiotensin-II-pharmacology; *Benzimidazoles-pharmacology; *Receptors,-Angiotensin-antagonists-and-inhibitors; *Tetrazoles-pharmacology
MESH: Angiotensin-II-antagonists-and-inhibitors; Blood-Pressure-drug-effects; Cats-; Dose-Response-Relationship,-Drug; Hindlimb-blood-supply; Time-Factors; Vasoconstrictor-Agents-pharmacology; Vasodilator-Agents-pharmacology
TG: Animal; Comparative-Study; Female; Male
PT: Journal-Article
SH: antagonists-and-inhibitors; pharmacology; drug-effects; blood-supply
RN: 0; 0; 0; 0; 0; 0; 11128-99-7; 139481-59-7
NM: Benzimidazoles; Receptors,-Angiotensin; Tetrazoles; Vasoconstrictor-Agents; Vasodilator-Agents; angiotensin-II-type-1-receptor; Angiotensin-II; CV-11974
SB: Index-Medicus
UD: 20001218
AN: 99107167
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 39 of 65 - MEDLINE (R) 1999 Part A
TI: Expression of the AT2 receptor developmentally programs extracellular signal-regulated kinase activity and influences fetal vascular growth.
AU: Akishita,-M; Ito,-M; Lehtonen,-J-Y; Daviet,-L; Dzau,-V-J; Horiuchi,-M
AD: Cardiovascular Research, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
SO: J-Clin-Invest. 1999 Jan; 103(1): 63-71
IS: 0021-9738
PY: 1999
LA: English
CP: UNITED-STATES
AB: Angiotensin II type 2 (AT2) receptor is abundantly expressed in vascular smooth muscle cells (VSMC) of the fetal vasculature during late gestation (embryonic day 15-20), during which the blood vessels undergo remodeling. To examine directly the influence of AT2 receptor expression in the developmental biology of VSMC, we studied cultures of VSMC from fetal and postnatal wild-type (Agtr2(+)) and AT2 receptor null (Agtr2(-)) mice. Consistent with in vivo data, AT2 receptor binding in cultured Agtr2(+) VSMC increased by age, peaking at embryonic day 20, and decreased dramatically after birth. Angiotensin II-induced growth in Agtr2(+) VSMC (embryonic day 20) was increased by the AT2 receptor blocker PD123319, indicating that the AT2 receptors are functional and exert an antigrowth effect in Agtr2(+) VSMC. Growth of VSMC in response to serum decreased age dependently and was higher in Agtr2(-) than in Agtr2(+), inversely correlating with AT2 receptor expression. However, serum-induced growth in Agtr2(+) and Agtr2(-) VSMC and the exaggerated Agtr2(-) VSMC growth was maintained even in the presence of PD123319 or losartan, an AT1 receptor blocker. Moreover, Agtr2(-) VSMC showed greater growth responses to platelet-derived growth factor and basic fibroblast growth factor, indicating that Agtr2(-) cells exhibit a generalized exaggerated growth phenotype. We studied the mechanism responsible for this phenotype and observed that extracellular signal-regulated kinase (ERK) activity was higher in Agtr2(-) VSMC at baseline and also in response to serum. ERK kinase inhibitor PD98059 inhibited both growth and ERK phosphorylation dose-dependently, while the regression lines between growth and ERK phosphorylation were identical in Agtr2(+) and Agtr2(-) VSMC, suggesting that increased ERK activity in Agtr2(-) VSMC is pivotal in the growth enhancement. Furthermore, the difference in ERK phosphorylation between Agtr2(+) and Agtr2(-) was abolished by vanadate but not by okadaic acid, implicating tyrosine phosphatase in the difference in ERK activity. These results suggest that the AT2 receptor expression during the fetal vasculogenesis influences the growth phenotype of VSMC via the modulation of ERK cascade.
MESH: *Blood-Vessels-growth-and-development; *Ca2+-Calmodulin-Dependent-Protein-Kinase-metabolism; *Gene-Expression-Regulation,-Developmental-genetics; *Receptors,-Angiotensin-genetics
MESH: Angiotensin-II-metabolism; Cell-Division-drug-effects; Cells,-Cultured; Culture-Media-pharmacology; DNA-biosynthesis; Flavones-pharmacology; Imidazoles-pharmacology; Losartan-pharmacology; Mice-; Mice,-Knockout; Muscle,-Smooth,-Vascular-growth-and-development; Okadaic-Acid-pharmacology; Phosphoproteins-analysis; Phosphorylation-; Protein-Binding; Pyridines-pharmacology; Receptors,-Angiotensin-metabolism; Vanadates-pharmacology
TG: Animal; Female; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: metabolism; growth-and-development; drug-effects; pharmacology; biosynthesis; genetics; analysis
RN: 0; 0; 0; 0; 0; 0; 0; 0; 11128-99-7; 114798-26-4; 130663-39-7; 78111-17-8; 9007-49-2; EC 2.7.10.-
NM: Culture-Media; Flavones; Imidazoles; PD-98059; Phosphoproteins; Pyridines; Receptors,-Angiotensin; Vanadates; Angiotensin-II; Losartan; PD-123319; Okadaic-Acid; DNA; Ca(2+)-Calmodulin-Dependent-Protein-Kinase
CN: HL35252HLNHLBI; HL35610HLNHLBI; HL46631HLNHLBI
SB: Abridged-Index-Medicus; Index-Medicus
UD: 20001218
AN: 99102249
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 40 of 65 - MEDLINE (R) 1999 Part A
TI: Efficacy and tolerability of tasosartan, a novel angiotensin II receptor blocker: results from a 10-week, double-blind, placebo-controlled, dose-titration study. Tasosartan Investigators Group.
AU: Neutel,-J-M; Buckalew,-V; Chrysant,-S-G; Mroczek,-W-J; Ruff,-D-A; Weber,-M
AD: University of California Irvine, USA.
SO: Am-Heart-J. 1999 Jan; 137(1): 118-25
IS: 0002-8703
PY: 1999
LA: English
CP: UNITED-STATES
AB: BACKGROUND: Angiotensin II receptor antagonists are selective blockers of the renin-angiotensin system and represent an alternative to angiotensin-converting enzyme inhibitors in the treatment of hypertension. Tasosartan is a newly developed nonpeptide AT1 receptor blocker. METHODS AND RESULTS: In this double-blind, randomized, dose-titration, multicenter trial, tasosartan and placebo were compared in patients with stage I and stage II hypertension. A prequalification washout period (antihypertensive medications withdrawn) and a 2-week qualification period (patients received single-blind placebo) preceded a 10-week, double-blind treatment period. The patients received either 50 mg tasosartan (n = 132) or placebo (n = 130) once per day and were evaluated once per week. The dose of tasosartan was increased at 3-week intervals to 100 mg and then to 200 mg if the mean sitting diastolic blood pressure (SiDBP) exceeded 90 mm Hg. Compared with placebo, tasosartan produced significantly (P <.05) greater reductions in both SiDBP (-9.4 +/- 0.7 vs -2.0 +/- 0.7 mm Hg) and sitting systolic blood pressure (SBP) (-12.2 +/- 1.2 vs +0.4 +/- 1.2 mm Hg). The rate of response (SiDBP </=90 mm Hg or a decrease from baseline of >/=10 mm Hg) was significantly (P <.05) greater in the tasosartan group than in the placebo group (55% vs 19%). The mean 24-hour blood pressure reduction with tasosartan was -12.6 +/- 0. 9/-8.1 +/- 0.6, significantly greater (P <.05) than the reduction with placebo (+0.6 +/- 0.9/+0.5 +/- 0.6 mm Hg). The trough-to-peak ratio (determined from the ambulatory data) was 0.66 for DBP and 0. 72 for SBP for the tasosartan treatment group, demonstrating 24-hour efficacy with once-a-day administration. The safety profile of tasosartan was similar to placebo. CONCLUSIONS: These results demonstrate that tasosartan at 50 to 200 mg given once a day over a titration period of 10 weeks was effective and safe in the treatment of essential hypertension.
MESH: *Blood-Pressure-drug-effects; *Hypertension-drug-therapy; *Pyrimidines-administration-and-dosage; *Receptors,-Angiotensin-antagonists-and-inhibitors; *Tetrazoles-administration-and-dosage
MESH: Adult-; Aged-; Blood-Pressure-Monitoring,-Ambulatory; Double-Blind-Method; Drug-Administration-Schedule; Hypertension-physiopathology; Middle-Age; Pyrimidines-blood; Severity-of-Illness-Index; Tetrazoles-blood; Treatment-Outcome; United-States
TG: Female; Human; Male; Support,-Non-U.S.-Gov't
PT: Clinical-Trial; Journal-Article; Multicenter-Study; Randomized-Controlled-Trial
SH: drug-effects; drug-therapy; physiopathology; administration-and-dosage; blood; antagonists-and-inhibitors
RN: 0; 0; 0; 0
NM: ANA-756; Pyrimidines; Receptors,-Angiotensin; Tetrazoles
SB: Abridged-Index-Medicus; Index-Medicus
UD: 20001218
AN: 99096434
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 41 of 65 - MEDLINE (R) 1998 Part B
TI: Effects of angiotensin II on expression of the gap junction channel protein connexin43 in neonatal rat ventricular myocytes.
AU: Dodge,-S-M; Beardslee,-M-A; Darrow,-B-J; Green,-K-G; Beyer,-E-C; Saffitz,-J-E
AD: Department of Pathology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA.
SO: J-Am-Coll-Cardiol. 1998 Sep; 32(3): 800-7
IS: 0735-1097
PY: 1998
LA: English
CP: UNITED-STATES
AB: OBJECTIVES: To elucidate signal transduction pathways regulating expression of myocardial gap junction channel proteins (connexins) and to determine whether mediators of cardiac hypertrophy might promote remodeling of gap junctions, we characterized the effects of angiotensin II on expression of the major cardiac gap junction protein connexin43 (Cx43) in cultured neonatal rat ventricular myocytes. BACKGROUND: Remodeling of the distribution of myocardial gap junctions appears to be an important feature of anatomic substrates of ventricular arrhythmias in patients with heart disease. Remodeling of intercellular connections may be initiated by changes in connexin expression caused by chemical mediators of the hypertrophic response. METHODS: Cultures were exposed to 0.1 micromol/liter angiotensin II for 6 or 24 h, and Cx43 expression was characterized by immunoblotting, confocal microscopy and electron microscopy. RESULTS: Immunoblot analysis revealed a twofold increase in Cx43 content in cells treated for 24 h with angiotensin II (n=4, p < 0.05). This response was inhibited by the presence of 1.0 micromol/liter losartan, an AT1-receptor blocker. Confocal and electron microscopy demonstrated enhanced Cx43 immunoreactivity and increases in the number and size of gap junction profiles in cells exposed to angiotensin II for 24 h. These effects were also blocked by losartan. Immunoprecipitation of Cx43 from cells metabolically labeled with [35S]methionine demonstrated 2.4- and 2.9-fold increases in Cx43 radioactivity after 6 and 24 h exposure to angiotensin II, respectively (p < 0.03 at each time point). CONCLUSIONS: Angiotensin II up-regulates gap junctions in cultured neonatal rat ventricular myocytes by increasing Cx43 synthesis. Signal transduction pathways activated by angiotensin II under pathophysiologic conditions could initiate remodeling of conduction pathways, leading to the development of anatomic substrates of arrhythmias.
MESH: *Angiotensin-II-physiology; *Cardiomegaly-physiopathology; *Connexin-43-physiology; *Heart-Ventricle-physiopathology; *Signal-Transduction-physiology
MESH: Animals,-Newborn; Cardiomegaly-pathology; Gap-Junctions-physiology; Gap-Junctions-ultrastructure; Heart-Ventricle-pathology; Microscopy,-Confocal; Microscopy,-Electron; Microscopy,-Fluorescence; Rats-; Tissue-Culture; Up-Regulation-Physiology-physiology
TG: Animal; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: physiology; pathology; physiopathology; ultrastructure
RN: 0; 11128-99-7
NM: Connexin-43; Angiotensin-II
CN: HL45466HLNHLBI; HL50598HLNHLBI
SB: Abridged-Index-Medicus; Index-Medicus
UD: 20001218
AN: 98412561
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 42 of 65 - MEDLINE (R) 1998 Part B
TI: Angiotensin II stimulation in vitro induces hypertrophy of normal and postinfarcted ventricular myocytes.
AU: Liu,-Y; Leri,-A; Li,-B; Wang,-X; Cheng,-W; Kajstura,-J; Anversa,-P
AD: Department of Medicine, New York Medical College, Valhalla 10595, USA.
SO: Circ-Res. 1998 Jun 15; 82(11): 1145-59
IS: 0009-7330
PY: 1998
LA: English
CP: UNITED-STATES
AB: To determine whether angiotensin II (Ang II) stimulation of adult ventricular myocytes in vitro results in cellular hypertrophy, the changes in myocyte volume and protein content per cell were examined by confocal microscopy. Moreover, the possibility was considered that the upregulation of Ang II receptors on myocytes after infarction may potentiate and/or accelerate Ang II-mediated myocyte growth. Left ventricular myocytes isolated from control and failing hearts 3 days after infarction were cultured for 3 and 7 days in the presence of Ang II. Normal myocytes did not show an increase in volume and protein content at 3 days, but a 16% and 20% increase in these respective parameters was found at 7 days. Cell growth was faster and greater in myocytes from postinfarcted hearts. In these cells, myocyte volume increased 23% and protein content increased 28% at 3 days after Ang II administration. The higher hypertrophic reaction of myocytes from infarcted hearts occurred in spite of a 19% larger volume at isolation. In both groups of myocytes, the AT1 receptor blocker losartan completely inhibited the consequences of Ang II. Conversely, the AT2 receptor antagonist PD123319 had no effect on Ang II-induced hypertrophy. In conclusion, Ang II promotes myocyte growth through the activation of AT1 receptors, which modulate the time and magnitude of this cellular response.
MESH: *Angiotensin-II-pharmacology; *Cardiomegaly-pathology; *Myocardial-Infarction-drug-therapy; *Myocardium-cytology; *Vasoconstrictor-Agents-pharmacology
MESH: Cardiomegaly-metabolism; Cell-Size-drug-effects; Cells,-Cultured; Microscopy,-Confocal; Muscle-Fibers-chemistry; Muscle-Fibers-cytology; Muscle-Fibers-drug-effects; Myocardial-Infarction-metabolism; Myocardial-Infarction-pathology; Myocardium-chemistry; Rats-; Rats,-Sprague-Dawley; Receptors,-Angiotensin-analysis; Receptors,-Angiotensin-metabolism; Up-Regulation-Physiology-drug-effects; Up-Regulation-Physiology-physiology; Ventricular-Function,-Left; Ventricular-Function,-Right
TG: Animal; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: pharmacology; metabolism; pathology; drug-effects; chemistry; cytology; drug-therapy; analysis; physiology
RN: 0; 0; 11128-99-7
NM: Receptors,-Angiotensin; Vasoconstrictor-Agents; Angiotensin-II
CN: HL38132HLNHLBI; HL39902HLNHLBI; HL43023HLNHLBI
SB: Index-Medicus
UD: 20001218
AN: 98295672
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 43 of 65 - MEDLINE (R) 1998 Part B
TI: Local angiotensin II generation in the rat heart: role of renin uptake.
AU: Muller,-D-N; Fischli,-W; Clozel,-J-P; Hilgers,-K-F; Bohlender,-J; Menard,-J; Busjahn,-A; Ganten,-D; Luft,-F-C
AD: Franz Volhard Clinic and the Max Delbruck Center for Molecular Medicine, Virchow Klinikum, Humboldt University of Berlin, Germany.
SO: Circ-Res. 1998 Jan 9-23; 82(1): 13-20
IS: 0009-7330
PY: 1998
LA: English
CP: UNITED-STATES
AB: To elucidate the local effects of renin in the coronary circulation, we examined local angiotensin (Ang) I and II formation, as well as coronary vasoconstriction in response to renin administration, and compared the effects with exogenous infused Ang I. We perfused isolated hearts from rats overexpressing the human angiotensinogen gene in a Langendorff preparation and measured the hemodynamic effects and the released products. We also investigated cardiac Ang I conversion, including the contribution of non-angiotensin-converting enzyme-dependent Ang II-generating pathways. Finally, we studied Ang I conversion in vitro in heart homogenates. Renin and Ang I infusion both generated Ang II. Ang II release and vasoconstriction continued after renin infusion was stopped, even though renin disappeared immediately from the perfusate. In contrast, after Ang I infusion, Ang II release and coronary flow returned to basal levels. Ang I conversion (Ang II/Ang I ratio) was higher after renin infusion (0.109+/-0.027 versus 0.026+/-0.003, 15 minutes, P<.02) compared with infused Ang I. Remikiren added to the renin infusion abolished Ang I and II; captopril suppressed only Ang II, whereas an AT1 receptor blocker did not affect Ang I and II formation. All the drugs prevented renin-induced coronary flow changes. Total cardiac Ang II-forming activity was only partially inhibited by cilazaprilat (4.1+/-0.1 fmol x min(-1) x mg[-1]) and on a larger extent by chymostatin (2.6+/-0.3 fmol x min(-1) x mg[-1]) compared with control values (5.6+/-0.4 fmol x min(-1) x mg[-1]). We conclude that renin can be taken up by cardiac or coronary vascular tissue and induces long-lasting local Ang II generation and vasoconstriction. Locally formed Ang I was converted more effectively than infused Ang I. Furthermore, the comparison of in vivo and in vitro Ang I conversion suggests that in vitro assays may underestimate the functional contribution of angiotensin-converting enzyme to intracardiac Ang II formation.
MESH: *Angiotensin-II-metabolism; *Myocardium-metabolism
MESH: Angiotensin-I-drug-effects; Angiotensin-I-metabolism; Angiotensin-I-pharmacology; Angiotensin-II-drug-effects; Angiotensin-Converting-Enzyme-Inhibitors-pharmacology; Antihypertensive-Agents-pharmacology; Blood-Flow-Velocity-drug-effects; Captopril-pharmacology; Coronary-Circulation-drug-effects; Coronary-Vessels-drug-effects; Coronary-Vessels-physiology; Heart-drug-effects; Imidazoles-pharmacology; Perfusion-; Protease-Inhibitors-pharmacology; Rats-; Rats,-Sprague-Dawley; Receptors,-Angiotensin-antagonists-and-inhibitors; Renin-administration-and-dosage; Renin-antagonists-and-inhibitors; Renin-pharmacokinetics; Serine-Endopeptidases-metabolism; Tetrazoles-pharmacology; Time-Factors; Vasoconstriction-drug-effects; Vasoconstriction-physiology
TG: Animal; Comparative-Study; Human; In-Vitro; Male; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: drug-effects; metabolism; pharmacology; physiology; antagonists-and-inhibitors; administration-and-dosage; pharmacokinetics
RN: 0; 0; 0; 0; 0; 0; 11128-99-7; 124750-92-1; 135669-48-6; 62571-86-2; 9041-90-1; EC 3.4.21; EC 3.4.21.39; EC 3.4.23.15
NM: Angiotensin-Converting-Enzyme-Inhibitors; Antihypertensive-Agents; Imidazoles; Protease-Inhibitors; Receptors,-Angiotensin; Tetrazoles; Angiotensin-II; EXP3174; Ro-42-5892; Captopril; Angiotensin-I; Serine-Endopeptidases; chymase; Renin
SB: Index-Medicus
UD: 20001218
AN: 98101650
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 44 of 65 - MEDLINE (R) 1998 Part B
TI: Endogenous angiotensin II and the reflex response to stimulation of cardiopulmonary serotonin 5HT3 receptors.
AU: Veelken,-R; Hilgers,-K-F; Scrogin,-K-E; Mann,-J-F; Schmieder,-R-E
AD: Department of Medicine-Nephrology, University of Erlangen-Nurnberg, Erlangen, Germany.
SO: Br-J-Pharmacol. 1998 Dec; 125(8): 1761-7
IS: 0007-1188
PY: 1998
LA: English
CP: ENGLAND
AB: 1. Angiotensin (Ang) II modulates cardiovascular baroreflexes; whether or not the peptide influences chemosensitive cardiovascular reflexes is not known. We tested the hypothesis that Ang II modulates the reflex control of sympathetic nerve activity exerted by 5-hydroxytryptamine 3 (5HT3) cardiopulmonary receptors. 2. The 5HT3 receptor agonist phenylbiguanide (PBG), infused intravenously for 15 min, elicited a sustained reflex decrease of renal sympathetic nerve activity (RSNA) but only transient (<3 min) changes of arterial blood pressure (BP) and heart rate (HR) in methohexital-anaesthesized rats. 3. Infusion of Ang II at a dose that did not affect baseline BP, HR and RSNA enhanced the PBG-evoked reflex decrease of RSNA (-54+/-5% in Ang II treated versus -33+/-6% in control rats after 15 min PBG, P<0.05, n = 6 each) in methohexital-anaesthetized rats. 4. The angiotensin converting enzyme (ACE) inhibitor lisinopril blunted the reflex responses to PBG in anaesthetized as well as conscious animals. The effect of the ACE inhibitor was abolished by concomitant infusion of Ang II. 5. The reflex response to stimulation of cardiopulmonary 5HT3 afferents was also impaired by the Ang II type 1 receptor (AT1) blocker ZD7155 but not by the type 2 (AT2) blocker PD 123319. 6. Infusion of a volume load to stimulate cardiopulmonary baroreceptors induced a gradual decrease of RSNA which was impaired by exogenous Ang II (RSNA -26+/-6% in Ang II treated versus -47+/-6% in control rats after volume load, P<0.05, n = 6 each) but unaffected by ACE inhibition. 7. The reflex control of RSNA by cardiopulmonary 5HT3 receptors is enhanced by Ang II via AT1 receptors. Thus, Ang II facilitates a chemosensitive cardiovascular reflex, in contrast to its inhibitory influences on mechanosensitive reflexes.
MESH: *Angiotensin-II-physiology; *Baroreflex-physiology; *Pressoreceptors-metabolism; *Receptors,-Serotonin-metabolism
MESH: Anesthesia-; Angiotensin-II-blood; Angiotensin-II-pharmacology; Angiotensin-Converting-Enzyme-Inhibitors-pharmacology; Baroreflex-drug-effects; Biguanides-pharmacology; Blood-Pressure-drug-effects; Heart-Rate-drug-effects; Imidazoles-pharmacology; Infusions,-Intravenous; Kidney-innervation; Lisinopril-pharmacology; Naphthyridines-pharmacology; Pressoreceptors-drug-effects; Pyridines-pharmacology; Rats-; Rats,-Sprague-Dawley; Receptors,-Angiotensin-antagonists-and-inhibitors; Receptors,-Serotonin-drug-effects; Serotonin-Agonists-pharmacology; Sodium-Chloride-pharmacology; Sympathetic-Nervous-System-drug-effects; Sympathetic-Nervous-System-physiology
TG: Animal; Male; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: blood; pharmacology; physiology; drug-effects; innervation; metabolism; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 102-02-3; 11128-99-7; 130663-39-7; 7647-14-5; 83915-83-7
NM: Angiotensin-Converting-Enzyme-Inhibitors; Biguanides; Imidazoles; Naphthyridines; Pyridines; Receptors,-Angiotensin; Receptors,-Serotonin; Serotonin-Agonists; ZD-7155; serotonin-3-receptor; phenyl-biguanide; Angiotensin-II; PD-123319; Sodium-Chloride; Lisinopril
SB: Index-Medicus
UD: 20001218
AN: 99101859
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 45 of 65 - MEDLINE (R) 1998 Part B
TI: Tolerability of a modern antihypertensive agent: candesartan cilexetil.
AU: Andersson,-O-K
AD: Department of Internal Medicine, Sahlgrenska University Hospital, Goteborg, Sweden.
SO: Basic-Res-Cardiol. 1998; 93 Suppl 254-8
IS: 0300-8428
PY: 1998
LA: English
CP: GERMANY
AB: Tolerability and not efficacy is the limiting factor for long-term successful antihypertensive treatment. Since the discontinuation rate of first line antihypertensives may be as high as 50-60% over six months, it is important to develop new agents with an improved efficacy/tolerability ratio. Candesartan cilexetil is particularly promising in this respect. Candesartan is a potent and selective angiotensin II type 1 (AT1) receptor blocker that binds selectively and tightly (insumontable binding) to the receptor. Candesartan is not associated with any increased risk of cough or angiodema. It is an orally effective vasodilator that does not cause reflex tachycardia or first dose hypotension or orthostatic hypotension. In the dose range from 4-16 mg, once daily candesartan cilexetil is not associated with any dose-dependent adverse events and it is equally well tolerated in men and women and by older (> 65 years) and younger (< 65 years) patients. Furthermore, the drug has no adverse effect on glucose homeostasis or plasma lipid profile. In a double-blind comparison with losartan 50 mg od, candesartan cilexetil 16 mg once daily was significantly more effective in lowering the diastolic blood pressure at the end of the 24 h dose interval but was equally well tolerated. In meta-analyses of clinical trials, candesartan cilexetil showed a tolerability profile comparable to that of placebo therapy.
MESH: *Antihypertensive-Agents-therapeutic-use; *Benzimidazoles-therapeutic-use; *Biphenyl-Compounds-therapeutic-use; *Prodrugs-therapeutic-use
MESH: Angiotensin-II-antagonists-and-inhibitors; Angiotensin-Converting-Enzyme-Inhibitors-therapeutic-use; Antihypertensive-Agents-adverse-effects; Benzimidazoles-adverse-effects; Biphenyl-Compounds-adverse-effects; Losartan-adverse-effects; Losartan-therapeutic-use; Prodrugs-adverse-effects; Randomized-Controlled-Trials
TG: Human
PT: Journal-Article; Review; Review,-Tutorial
SH: antagonists-and-inhibitors; therapeutic-use; adverse-effects
RN: 0; 0; 0; 0; 0; 11128-99-7; 114798-26-4; 145040-37-5
NM: Angiotensin-Converting-Enzyme-Inhibitors; Antihypertensive-Agents; Benzimidazoles; Biphenyl-Compounds; Prodrugs; Angiotensin-II; Losartan; TCV-116
SB: Index-Medicus
UD: 20001218
AN: 99050358
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 46 of 65 - MEDLINE (R) 1998 Part B
TI: Chronic effects of early started angiotensin converting enzyme inhibition and angiotensin AT1-receptor subtype blockade in rats with myocardial infarction: role of bradykinin.
AU: Hu,-K; Gaudron,-P; Anders,-H-J; Weidemann,-F; Turschner,-O; Nahrendorf,-M; Ertl,-G
AD: II. Medizinische Klinik, Klinikum Mannheim, Universitat Heidelberg, Germany.
SO: Cardiovasc-Res. 1998 Aug; 39(2): 401-12
IS: 0008-6363
PY: 1998
LA: English
CP: NETHERLANDS
AB: OBJECTIVE: The long-term effects and mechanisms of early started angiotensin converting enzyme (ACE) inhibition post myocardial infarction (MI) are not well understood. Chronic effects of early ACE inhibition on hemodynamics, left ventricular diastolic wall stress and remodeling were, therefore, compared to that of angiotensin AT1-receptor subtype blockade in rats with experimental myocardial infarction. The contribution of bradykinin potentiation to both ACE inhibitor and angiotensin AT1-receptor subtype blockade was assessed by cotreatment of rats with a bradykinin B2-receptor antagonist. METHODS: MI was produced by coronary artery ligation in adult male Wistar rats. The ACE inhibitor, quinapril (6 mg/kg per day), or the angiotensin AT1-receptor subtype blocker, losartan (10 mg/kg per day), administered by gavage, and the bradykinin B2-receptor antagonist, Hoe-140 (500 micrograms/kg per day s.c.), administered either alone or in combination with quinapril or losartan, were started 30 min after MI and continued for eight weeks. RESULTS: Quinapril and losartan reduced left ventricular end-diastolic pressure and global left ventricular diastolic wall stress only in rats with large MI. Pressure volume curves showed a rightward shift in proportion to MI size that was not prevented by quinapril or losartan treatment. Only the ACE inhibitor reduced left ventricular weight and this effect was prevented by cotreatment with the bradykinin antagonist. Baseline and peak cardiac index and stroke volume index, as determined using an electromagnetic flowmeter before and after an acute intravenous volume load, were restored by quinapril, whereas losartan had no effects. CONCLUSION: Treatments starting 30 min after coronary artery ligation, with either quinapril or losartan, reduced preload only in rats with large MI. Despite this unloading of the heart, structural dilatation was not prevented by this early treatment. Only quinapril improved cardiac performance and reduced left ventricular weight and this effect was abolished by cotreatment with Hoe-140, suggesting an angiotensin II blockade-independent, but bradykinin potentiation-dependent, mechanism.
MESH: *Angiotensin-I-pharmacology; *Angiotensin-Converting-Enzyme-Inhibitors-therapeutic-use; *Isoquinolines-therapeutic-use; *Losartan-therapeutic-use; *Myocardial-Infarction-drug-therapy; *Receptors,-Angiotensin-antagonists-and-inhibitors
MESH: Adrenergic-beta-Antagonists-pharmacology; Analysis-of-Variance; Bradykinin-analogs-and-derivatives; Bradykinin-metabolism; Bradykinin-pharmacology; Dose-Response-Relationship,-Drug; Heart-Ventricle-pathology; Heart-Ventricle-physiopathology; Hemodynamics-drug-effects; Hypertrophy,-Left-Ventricular-prevention-and-control; Myocardial-Infarction-metabolism; Organ-Weight-drug-effects; Rats-; Rats,-Wistar; Receptors,-Bradykinin-antagonists-and-inhibitors
TG: Animal; Comparative-Study; Male
PT: Journal-Article
SH: pharmacology; therapeutic-use; analogs-and-derivatives; metabolism; pathology; physiopathology; drug-effects; prevention-and-control; drug-therapy; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 0; 114798-26-4; 130308-48-4; 58-82-2; 82586-55-8; 9041-90-1
NM: Adrenergic-beta-Antagonists; Angiotensin-Converting-Enzyme-Inhibitors; Isoquinolines; Receptors,-Angiotensin; Receptors,-Bradykinin; Losartan; icatibant; Bradykinin; quinapril; Angiotensin-I
SB: Index-Medicus
UD: 20001218
AN: 99015259
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 47 of 65 - MEDLINE (R) 1998 Part B
TI: Angiotensin II induces superoxide anion production by mesangial cells.
AU: Jaimes,-E-A; Galceran,-J-M; Raij,-L
AD: Nephrology and Hypertension Section, Veterans Administration Medical Center and University of Minnesota, Minneapolis 55417, USA.
SO: Kidney-Int. 1998 Sep; 54(3): 775-84
IS: 0085-2538
PY: 1998
LA: English
CP: UNITED-STATES
AB: BACKGROUND: The recognized role of angiotensin II (Ang II) in the pathogenesis of the progression of renal disease cannot be solely attributed to Ang II's hemodynamic effects. Indeed, growth stimulating signals driven by Ang II promote mesangial cell (MC) hypertrophy and extracellular matrix production, prominent features of progressive glomerular injury. Superoxide anion (O2-) avidly interacts with nitric oxide, an endogenous vasodilator that inhibits growth factor stimulated MC growth and matrix production. In addition, O2- acting as an intracellular signal is linked to growth related responses such as activation of mitogen activated protein (MAP) kinases. The studies reported herein were designed to investigate: (a) whether Ang II induces MC O2-production and (b) if increased O2- production elicits growth responses in MC. METHODS: MC were exposed to Ang II for 24 or 48 hours. In some experiments, in addition to Ang II, MC were exposed to: diphenylenieodonium (DPI), an inhibitor of the flavin containing NADH/NADPH oxidase; losartan (LOS), an Ang II type 1 (AT1) receptor blocker; PD 98059, a MAP kinases inhibitor; the protein kinase C inhibitors Calphostin C or H-7; and the tyrosine kinase inhibitors, herbymycin A or genistein. RESULTS: Ang II (10(-5) M to 10(-8) M) dose dependently increased MC O2- production up to 125% above control (ED 50 5 x 10(-7) M). LOS as well as DPI, and the PKC inhibitors blocked Ang II stimulated MC O2- production. Ang II dose dependently increased MC 3H-leucine incorporation, and MC protein content, two markers of MC hypertrophy, as well as 3H-thymidine incorporation, a marker of MC hyperplasia. PD98059, a specific inhibitor of MAP kinases prevented Ang II induced MC hypertrophy. Moreover, LOS, DPI, and the PKC inhibitors each independently inhibited MC 3H-leucine incorporation, thereby establishing the specificity of Ang II induced O2- in driving MC hypertrophy. CONCLUSIONS: The current studies demonstrate a previously unrecognized link between Ang II and MC O2- production that may participate in the pathophysiology of progressive renal disease by concomitantly affecting the hemodynamics of the glomerular microcirculation as well as growth related responses of MC to injury.
MESH: *Angiotensin-II-pharmacology; *Glomerular-Mesangium-drug-effects; *Superoxides-metabolism
MESH: Angiotensin-Converting-Enzyme-Inhibitors-pharmacology; Glomerular-Mesangium-metabolism; Glomerular-Mesangium-pathology; Multienzyme-Complexes-metabolism; NADH,-NADPH-Oxidoreductases-metabolism; Rats-; Rats,-Sprague-Dawley; Reactive-Oxygen-Species
TG: Animal; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.
PT: Journal-Article
SH: pharmacology; drug-effects; metabolism; pathology
RN: 0; 0; 0; 11062-77-4; 11128-99-7; EC 1.6.; EC 1.6.-
NM: Angiotensin-Converting-Enzyme-Inhibitors; Multienzyme-Complexes; Reactive-Oxygen-Species; Superoxides; Angiotensin-II; NADH,-NADPH-Oxidoreductases; NADH2-oxidase
SB: Index-Medicus
UD: 20001218
AN: 98403671
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 48 of 65 - MEDLINE (R) 1998 Part A
TI: Role of NADH/NADPH oxidase-derived H2O2 in angiotensin II-induced vascular hypertrophy.
AU: Zafari,-A-M; Ushio-Fukai,-M; Akers,-M; Yin,-Q; Shah,-A; Harrison,-D-G; Taylor,-W-R; Griendling,-K-K
AD: From the Department of Medicine, Division of Cardiology, Emory University, Atlanta, GA 30322, USA.
SO: Hypertension. 1998 Sep; 32(3): 488-95
IS: 0194-911X
PY: 1998
LA: English
CP: UNITED-STATES
AB: Recent evidence suggests that oxidative mechanisms may be involved in vascular smooth muscle cell (VSMC) hypertrophy. We previously showed that angiotensin II (Ang II) increases superoxide production by activating an NADH/NADPH oxidase, which contributes to hypertrophy. In this study, we determined whether Ang II stimulation of this oxidase results in H2O2 production by studying the effects of Ang II on intracellular H2O2 generation, intracellular superoxide dismutase and catalase activity, and hypertrophy. Ang II (100 nmol/L) significantly increased intracellular H2O2 levels at 4 hours. Neither superoxide dismutase activity nor catalase activity was affected by Ang II; the SOD present in VSMCs is sufficient to metabolize Ang II-stimulated superoxide to H2O2, which accumulates more rapidly than it is degraded by catalase. This increase in H2O2 was inhibited by extracellular catalase, diphenylene iodonium, an inhibitor of the NADH/NADPH oxidase, and the AT1 receptor blocker losartan. In VSMCs stably transfected with antisense p22phox, a critical component of the NADH/NADPH oxidase in which oxidase activity was markedly reduced, Ang II-induced production of H2O2 was almost completely inhibited, confirming that the source of Ang II-induced H2O2 was the NADH/NADPH oxidase. Using a novel cell line that stably overexpresses catalase, we showed that this increased H2O2 is a critical step in VSMC hypertrophy, a hallmark of many vascular diseases. Inhibition of intracellular superoxide dismutase by diethylthiocarbamate (1 mmol/L) also resulted in attenuation of Ang II-induced hypertrophy (62+/-2% inhibition). These data indicate that AT1 receptor-mediated production of superoxide generated by the NADH/NADPH oxidase is followed by an increase in intracellular H2O2, suggesting a specific role for these oxygen species and scavenging systems in modifying the intracellular redox state in vascular growth.
MESH: *Angiotensin-II-pharmacology; *Hydrogen-Peroxide-metabolism; *Muscle,-Smooth,-Vascular-enzymology; *NADH,-NADPH-Oxidoreductases-physiology; *Oxidants-metabolism; *Vasoconstrictor-Agents-pharmacology
MESH: Angiotensin-II-adverse-effects; Catalase-drug-effects; Catalase-metabolism; Cells,-Cultured; Hypertrophy-chemically-induced; Muscle,-Smooth,-Vascular-drug-effects; Muscle,-Smooth,-Vascular-metabolism; NADH,-NADPH-Oxidoreductases-drug-effects; RNA,-Messenger-isolation-and-purification; Rats-; Superoxide-Dismutase-drug-effects; Superoxide-Dismutase-metabolism
TG: Animal; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: adverse-effects; pharmacology; drug-effects; metabolism; chemically-induced; enzymology; physiology; isolation-and-purification
RN: 0; 0; 0; 11128-99-7; 7722-84-1; EC 1.11.1.6; EC 1.15.1.1; EC 1.6.
NM: Oxidants; RNA,-Messenger; Vasoconstrictor-Agents; Angiotensin-II; Hydrogen-Peroxide; Catalase; Superoxide-Dismutase; NADH,-NADPH-Oxidoreductases
CN: HL38206HLNHLBI
SB: Index-Medicus
UD: 20001218
AN: 98413202
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 49 of 65 - MEDLINE (R) 1998 Part A
TI: Safety of irbesartan in the treatment of mild to moderate systemic hypertension.
AU: Simon,-T-A; Gelarden,-R-T; Freitag,-S-A; Kassler-Taub,-K-B; Davies,-R
AD: Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 18543-4000, USA.
SO: Am-J-Cardiol. 1998 Jul 15; 82(2): 179-82
IS: 0002-9149
PY: 1998
LA: English
CP: UNITED-STATES
AB: Nine multicenter, randomized, placebo-controlled studies were conducted to evaluate the safety and tolerability of the angiotensin II subtype 1 receptor blocker (AT1 blocker) irbesartan for the treatment of mild to moderate hypertension. After a 4- to 5-week placebo lead-in phase, patients were randomized to 4 to 12 weeks of double-blind therapy with either placebo (n = 641) or irbesartan (n = 1,965) at doses of 1 to 900 mg orally. All doses of irbesartan were well tolerated with no evidence of dose-related adverse effects. Across the full recommended clinical dose range, although not statistically significantly different, irbesartan use was associated with a lower incidence of adverse events, serious adverse events, and discontinuations due to adverse events compared with placebo. No clinically significant or unexpected changes in laboratory analyses were observed. Withdrawal of irbesartan therapy did not result in rebound hypertension or clinically important adverse events. Thus, irbesartan use in hypertensive patients was associated with a placebo-like safety and tolerability profile.
MESH: *Antihypertensive-Agents-administration-and-dosage; *Antihypertensive-Agents-adverse-effects; *Biphenyl-Compounds-administration-and-dosage; *Biphenyl-Compounds-adverse-effects; *Hypertension-drug-therapy; *Tetrazoles-administration-and-dosage; *Tetrazoles-adverse-effects
MESH: Adult-; Aged-; Double-Blind-Method; Drug-Administration-Schedule; Middle-Age; Severity-of-Illness-Index; Treatment-Outcome
TG: Female; Human; Male
PT: Clinical-Trial; Journal-Article; Multicenter-Study; Randomized-Controlled-Trial
SH: administration-and-dosage; adverse-effects; drug-therapy
RN: 0; 0; 0; 138402-11-6
NM: Antihypertensive-Agents; Biphenyl-Compounds; Tetrazoles; irbesartan
SB: Abridged-Index-Medicus; Index-Medicus
UD: 20001218
AN: 98341428
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 50 of 65 - MEDLINE (R) 1998 Part A
TI: Angiotensin AT1B receptor mediates calcium signaling in vascular smooth muscle cells of AT1A receptor-deficient mice.
AU: Zhu,-Z; Zhang,-S-H; Wagner,-C; Kurtz,-A; Maeda,-N; Coffman,-T; Arendshorst,-W-J
AD: Department of Physiology, University of North Carolina at Chapel Hill, 27599-7545, USA.
SO: Hypertension. 1998 May; 31(5): 1171-7
IS: 0194-911X
PY: 1998
LA: English
CP: UNITED-STATES
AB: Our studies on angiotensin II receptor subtype 1A (AT1A) knockout mice define how endogenous receptors other than AT1A receptors stimulate changes in cytosolic calcium concentration ([Ca2+]i) in cultured aortic vascular smooth muscle cells (VSMCs). Wild-type cells have a 1.7 ratio of AT1A/AT1B receptor mRNA as determined by semiquantitative reverse transcriptase-polymerase chain reaction. Mutant cells express AT1B receptor mRNA but not that for the AT1A receptor. In wild-type cells with AT1A present, Ang II (10(-7) mol/L) produces a characteristic rapid peak increase in [Ca2+]i of 150 to 180 nmol/L, followed by a plateau phase characterized by a sustained 70 to 80 nmol/L increase in [Ca2+]i. An unexpected finding was that the magnitude and time-dependent pattern of [Ca2+]i changes produced by Ang II were similar in cells that lacked AT1A receptors but possessed AT1B receptors. The response in mutant cells indicates effective coupling of an Ang II receptor to one or more second messenger systems. The similarity of response patterns between cells with and without AT1A receptors suggests that non-AT1A receptors are functionally linked to similar signal transduction pathways in mutant cells. The fact that mutant and wild-type cells exhibit similar patterns of calcium mobilization and entry supports the notion that AT1A and non-AT1A receptors share common signal transduction pathways. The AT2 receptor ligands PD-123319 and CGP-42112 do not alter Ang II effects in either VSMC type, suggesting a paucity of AT2 receptors and/or an absence of their linkage to [Ca2+]i pathways. The nonpeptide AT1 receptor blocker losartan antagonizes Ang II-induced [Ca2+]i increases in both cell groups, supporting mediation by native AT1B receptors and effective coupling of this subtype to second messenger systems leading to calcium entry and mobilization. Our results demonstrate that Ang II causes calcium signaling in AT1A-deficient VSMCs that is mediated by an endogenous losartan-sensitive AT1B receptor.
MESH: *Angiotensin-II-metabolism; *Aorta-metabolism; *Calcium-metabolism; *Muscle,-Smooth,-Vascular-metabolism; *Receptors,-Angiotensin-deficiency; *Receptors,-Angiotensin-genetics; *Signal-Transduction
MESH: Cells,-Cultured; Mice-; Mice,-Knockout; Mutation-
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: metabolism; deficiency; genetics
RN: 0; 11128-99-7; 7440-70-2
NM: Receptors,-Angiotensin; Angiotensin-II; Calcium
CN: HL02334HLNHLBI; HL56122HLNHLBI
SB: Index-Medicus
UD: 20001218
AN: 98235664
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 51 of 65 - MEDLINE (R) 1998 Part A
TI: Link between angiotensin II and TGF-beta in the kidney.
AU: Wolf,-G
AD: Department of Medicine, University of Hamburg, Germany. wolf@uke.uni-hamburg.de
SO: Miner-Electrolyte-Metab. 1998; 24(2-3): 174-80
IS: 0378-0392
PY: 1998
LA: English
CP: SWITZERLAND
AB: Glomerulosclerosis and tubulointerstitial fibrosis are common morphological correlates of many end-stage kidneys. There is ample evidence that transforming growth factor-beta (TGF-beta) plays a major role in these alterations by directly stimulating synthesis of many extracellular matrix components and reducing collagenase production, finally leading to renal scarring. Although many factors may induce TGF-beta expression in the kidney, one very interesting aspect is the link between angiotensin II (ANG II) and TGF-beta. Originating from observations in vascular smooth muscle cells, there are now several additional studies showing that ANG II stimulates TGF-beta expression in the kidney. Although cell culture studies have convincingly demonstrated that the vasoactive peptide directly stimulates transcription as well as bioactivation of TGF-beta, the in vivo evidence is more indirect. Nevertheless, there are several pathophysiological situations including unilateral ureteral obstruction, chronic cyclosporin A nephrotoxicity, various models of hypertension, and probably diabetic nephropathy in which ANG II-mediated TGF-beta induction has been demonstrated to play an important role in the progression of the disease. The fascinating aspect of this relationship between ANG II and TGF-beta is the fact that hemodynamic changes as well as structural changes are linked together generating a unifying model of progression of chronic renal failure with ANG II as the key player. Angiotensin-converting enzyme (ACE) inhibitor and the more recently introduced AT1-receptor blocker may be potential drugs to interfere with this ANG II-mediated TGF-beta expression. Therefore, these drugs should not only be considered as antihypertensive medications, but should rather be viewed as renoprotective substances influencing renal remodeling by preventing local TGF-beta expression.
MESH: *Angiotensin-II-physiology; *Kidney-Failure,-Chronic-metabolism; *Kidney-Failure,-Chronic-pathology; *Transforming-Growth-Factor-beta-physiology
MESH: Angiotensin-II-pharmacology; Gene-Expression-drug-effects; Kidney-metabolism; Kidney-pathology; Transforming-Growth-Factor-beta-genetics
TG: Animal; Human; Support,-Non-U.S.-Gov't
PT: Journal-Article; Review; Review,-Tutorial
SH: pharmacology; physiology; drug-effects; metabolism; pathology; genetics
RN: 0; 11128-99-7
NM: Transforming-Growth-Factor-beta; Angiotensin-II
SB: Index-Medicus
UD: 20001218
AN: 98184615
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 52 of 65 - MEDLINE (R) 1998 Part A
TI: Role of AT1 receptors in the renal papillary effects of acute and chronic nitric oxide inhibition.
AU: Ortiz,-M-C; Fortepiani,-L-A; Ruiz-Marcos,-F-M; Atucha,-N-M; Garcia-Estan,-J
AD: Departamento de Fisiologia, Facultad de Medicina, Murcia, Spain.
SO: Am-J-Physiol. 1998 Mar; 274(3 Pt 2): R760-6
IS: 0002-9513
PY: 1998
LA: English
CP: UNITED-STATES
AB: Nitric oxide (NO) is a vasodilator substance controlling renal papillary blood flow (PBF) in the rat. In this study we have evaluated the role of AT1 angiotensin II receptors as modulators of the whole kidney and papillary vasoconstrictor effects induced by the acute or chronic inhibition of NO synthesis. Experiments have been performed in anesthetized, euvolemic Munich-Wistar rats prepared for the study of renal blood flow (RBF) and PBF. In normal rats, acute administration of the NO synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) increased mean arterial pressure (MAP) and decreased RBF and PBF. Either acute or chronic treatment with the AT1 receptor blocker losartan did not modify the decreases in RBF or PBF secondary to L-NAME. In animals made hypertensive by chronic inhibition of NO, basal MAP was higher, whereas RBF and PBF were lower than in the controls. In these animals, acute or chronic administration of losartan decreased MAP and increased both RBF and PBF significantly. These results indicate that, under normal conditions, the decreases in RBF or PBF induced by the acute inhibition of NO synthesis are not modulated by AT1-receptor stimulation. However, the arterial hypertension, renal vasoconstriction, and reduced PBF present in chronic NO-deficient hypertensive rats is partially due to the effects of angiotensin II, via stimulation of AT1-receptors.
MESH: *Enzyme-Inhibitors-pharmacology; *Kidney-Medulla-blood-supply; *Losartan-pharmacology; *NG-Nitroarginine-Methyl-Ester-pharmacology; *Nitric-Oxide-Synthase-antagonists-and-inhibitors; *Receptors,-Angiotensin-antagonists-and-inhibitors
MESH: Angiotensin-II-physiology; Blood-Pressure-drug-effects; Kidney-Medulla-physiology; Rats-; Regional-Blood-Flow-drug-effects
TG: Animal; Male; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: physiology; drug-effects; pharmacology; blood-supply; antagonists-and-inhibitors
RN: 0; 0; 0; 11128-99-7; 114798-26-4; 50903-99-6; EC 1.14.13.39
NM: Enzyme-Inhibitors; Receptors,-Angiotensin; angiotensin-II-type-1-receptor; Angiotensin-II; Losartan; NG-Nitroarginine-Methyl-Ester; Nitric-Oxide-Synthase
SB: Index-Medicus
UD: 20001218
AN: 98191275
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 53 of 65 - MEDLINE (R) 1997 Part B
TI: Angiotensin II inhibits inducible nitric oxide synthase in tubular MCT cells by a posttranscriptional mechanism.
AU: Wolf,-G; Ziyadeh,-F-N; Schroeder,-R; Stahl,-R-A
AD: Department of Medicine, University of Hamburg, Germany.
SO: J-Am-Soc-Nephrol. 1997 Apr; 8(4): 551-7
IS: 1046-6673
PY: 1997
LA: English
CP: UNITED-STATES
AB: Expression of the inducible isoform of nitric oxide synthase (iNOS) and generation of nitric oxide (NO) have been recently described, in addition to mesangial and medullary thick ascending limb cells, in proximal tubular cells, including MCT, a mouse proximal tubular epithelium cell line. Because vasoconstrictors may interfere with the induction of iNOS and the subsequent generation of NO, in the study presented here, whether exogenous angiotensin II (ANG II) influences bacterial lipopolysaccharide (LPS)/gamma-interferon (gamma-IF)-stimulated NO synthesis and iNOS protein and mRNA expression in MCT cells was tested. LPS/gamma-IF readily stimulated nitrite synthesis in MCT cells, as one measured parameter of NO synthesis. Coincubation of cells with 10(-9)-10(-6) M ANG II attenuated this LPS/gamma-IF-stimulated induction of nitrite. This effect was reversed by the AT1-receptor blocker losartan, but not by an AT2-receptor antagonist, indicating signal transduction through AT1-receptors. Western blot analysis applying a specific monoclonal antibody generated against mouse iNOS revealed that 10(-8)-10(-6) M ANG II significantly reduced LPS/gamma-IF-induced iNOS protein expression. However, ANG II had no effect on LPS/gamma-IF-induced iNOS mRNA as assessed by Northern blots. Moreover, transient transfection studies using a chimeric gene construct, in which iNOS regulatory elements are linked to the CAT reporter gene, showed no effect of ANG II on the LPS/gamma-IF-stimulated transcriptional activity. The study presented here demonstrates that ANG II influences LPS/gamma-IF-stimulated NO generation in MCT cells, most likely at a posttranscriptional level, by influencing iNOS protein expression. Whether proximal tubular cells in vivo express iNOS remains to be established, but this study suggests a mechanism for how iNOS activity is influenced by ANG II in cultured proximal tubular cells.
MESH: *Angiotensin-II-metabolism; *Gene-Expression-Regulation,-Enzymologic; *Kidney-Tubules,-Collecting-metabolism; *Nitric-Oxide-biosynthesis; *Nitric-Oxide-Synthase-biosynthesis; *RNA-Processing,-Post-Transcriptional; *RNA,-Messenger-metabolism
MESH: Blotting,-Northern; Blotting,-Western; Cell-Line; Interferon-Type-II-metabolism; Kidney-Tubules,-Collecting-cytology; Kidney-Tubules,-Collecting-enzymology; Lipopolysaccharides-metabolism; Mice-; Nitric-Oxide-Synthase-genetics; RNA,-Messenger-drug-effects
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: metabolism; cytology; enzymology; biosynthesis; genetics; drug-effects
RN: 0; 0; 10102-43-9; 11128-99-7; 82115-62-6; EC 1.14.13.-; EC 1.14.13.39
NM: Lipopolysaccharides; RNA,-Messenger; Nitric-Oxide; Angiotensin-II; Interferon-Type-II; inducible-nitric-oxide-synthase; Nitric-Oxide-Synthase
CN: DK44513DKNIDDK; DK45191DKNIDDK
SB: Index-Medicus
UD: 20001218
AN: 99425791
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 54 of 65 - MEDLINE (R) 1997 Part B
TI: Irbesartan--ein neuer AT1-Rezeptor-Antagonist (AT1-Blocker). Angiotensin-II-Rezeptor-Antagonisten: Perspektiven eines neuen Therapieprinzips Wiesbaden, 6. April 1997.
[Irbesartan--a new AT1-receptor antagonist (AT1-blocker). Angiotensin-II-receptor antagonists: perspectives of a new therapeutic principle, Wiesbaden, 6 April 1997]
AU: Anonymous
SO: Dtsch-Med-Wochenschr. 1997 Sep; 122(37 Suppl): 1-4
IS: 0012-0472
PY: 1997
LA: German; Non-English
CP: GERMANY
MESH: *Angiotensin-I-antagonists-and-inhibitors; *Antihypertensive-Agents-therapeutic-use; *Biphenyl-Compounds-therapeutic-use; *Receptors,-Angiotensin-antagonists-and-inhibitors; *Tetrazoles-therapeutic-use
MESH: Hypertension-drug-therapy
TG: Human
PT: Congresses
SH: antagonists-and-inhibitors; therapeutic-use; drug-therapy
RN: 0; 0; 0; 0; 138402-11-6; 9041-90-1
NM: Antihypertensive-Agents; Biphenyl-Compounds; Receptors,-Angiotensin; Tetrazoles; irbesartan; Angiotensin-I
SB: Index-Medicus
UD: 20001218
AN: 97471638
--------------------------------------------------------------------------------
Record 55 of 65 - MEDLINE (R) 1997 Part B
TI: The subtype 2 angiotensin receptor regulates renal prostaglandin F2 alpha formation in conscious rats.
AU: Siragy,-H-M; Carey,-R-M
AD: Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
SO: Am-J-Physiol. 1997 Sep; 273(3 Pt 2): R1103-7
IS: 0002-9513
PY: 1997
LA: English
CP: UNITED-STATES
AB: The angiotensin AT1 receptor mediates renal prostaglandin (PG) E2 production through stimulation of phospholipase A2. Blockade of the AT2 receptor potentiates the angiotensin II-induced increase in PGE2 levels. In the kidney, PGE2 is converted to PGF2 alpha mainly by the enzyme PGE 9-ketoreductase. We hypothesized that the conversion of PGE2 to PGF2 alpha is inhibited by AT2 receptor blockade, resulting in the observed increase in PGE2 levels. Using a microdialysis technique, we monitored changes in renal interstitial fluid PGE2 and PGF2 alpha in response to 5 days of sodium depletion alone or a combination of sodium depletion and intravenous infusion of the AT1 receptor blocker losartan or the AT2 receptor blocker PD-123319 in conscious rats. We utilized the PGF2 alpha-to-PGE2 ratio as an indirect measure of the rate of renal PGF2 alpha formation. Sodium depletion increased PGE2, PGF2 alpha, and the PGF2 alpha-to-PGE2 ratio. During sodium depletion, losartan decreased PGE2 and PGF2 alpha and did not change the PGF2 alpha-to-PGE2 ratio. In contrast, PD-123319 increased PGE2, decreased PGF2 alpha, and decreased the PGF2 alpha-to-PGE2 ratio. These data demonstrate that activation of the renin-angiotensin system during sodium depletion physiologically increases renal conversion of PGE2 to PGF2 alpha. The increase in renal production of PGF2 alpha is mediated through stimulation of the angiotensin AT2 receptor.
MESH: *Biphenyl-Compounds-pharmacology; *Dinoprost-metabolism; *Imidazoles-pharmacology; *Kidney-physiology; *Receptors,-Angiotensin-physiology; *Tetrazoles-pharmacology
MESH: Angiotensin-II-pharmacology; Blood-Pressure-drug-effects; Diet,-Sodium-Restricted; Dinoprostone-metabolism; Extracellular-Space-physiology; Homeostasis-; Kidney-drug-effects; Losartan-; Microdialysis-; Rats-; Rats,-Sprague-Dawley; Receptors,-Angiotensin-antagonists-and-inhibitors; Sodium,-Dietary
TG: Animal; Female; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: pharmacology; drug-effects; metabolism; physiology; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 0; 0; 11128-99-7; 114798-26-4; 363-24-6; 551-11-1
NM: Biphenyl-Compounds; Imidazoles; Receptors,-Angiotensin; Sodium,-Dietary; Tetrazoles; angiotensin-II-type-1-receptor; Angiotensin-II; Losartan; Dinoprostone; Dinoprost
CN: HL47669HLNHLBI; HL49575HLNHLBI; HL57503HLNHLBI
SB: Index-Medicus
UD: 20001218
AN: 97463108
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 56 of 65 - MEDLINE (R) 1997 Part B
TI: Angiotensin II and myocyte growth: role of fibroblasts.
AU: Sil,-P; Sen,-S
AD: Department of Molecular Cardiology, Research Institute, The Cleveland Clinic Foundation Ohio 44195, USA.
SO: Hypertension. 1997 Aug; 30(2 Pt 1): 209-16
IS: 0194-911X
PY: 1997
LA: English
CP: UNITED-STATES
AB: Angiotensin II (Ang II) has been implicated in stimulating myocyte growth in vitro, but the mechanism for such stimulation is still an open question. To understand the role of Ang II, we studied its effect on protein synthesis in rat neonatal and adult myocytes. Ang II (10(-8) mol/L) stimulated protein synthesis in neonatal myocytes by 43+/-3.5% over control. To prevent the proliferation of fibroblasts, bromodeoxyuridine was added, and protein synthesis in neonatal myocytes was reduced to 21+/-2.2% over control. In adult myocytes (cultured without bromodeoxyuridine), Ang II stimulated [3H]leucine incorporation by 24+/-2.3% over control; with bromodeoxyuridine, that stimulation was reduced significantly (13+/-0.93% over control). These data suggest that the presence of fibroblasts in the cultures may control myocyte growth. When supernatant from pure fibroblast culture was added to myocyte preparations, a significant increase (49.8+/-3.5% over control) in protein synthesis occurred. Pretreatment of these fibroblasts with Ang II (10(-3) mol/L) further stimulated protein synthesis, suggesting that Ang II directly stimulates the production of a factor from fibroblasts. The stimulatory effect of Ang II on the release of the factor can be completely blocked by pretreatment with losartan, an Ang II receptor (AT1) blocker. Our data are the first to demonstrate a paracrine effect of a fibroblast-derived factor that modulates myocyte growth. Fibroblast-derived factor loses its biological activity by (1) tryptic digestion, (2) exposure to pH below 4.0 and above 9.0, and (3) heating to 95 degrees C. The molecular weight of the factor is approximately 65 kD. The antibodies against fibroblast growth factor (both acidic and basic) could not inhibit this factor's stimulatory effect. Furthermore, this factor is heart specific and is produced at least up to the 16th passage of neonatal rat heart fibroblasts. Skin fibroblasts, aortic endothelial cells, and aortic smooth muscle cells do not produce this protein. Our data suggest that the observed myocyte growth by Ang II comes about via fibroblast-derived factor, which is increased by Ang II. Cross talk between fibroblasts and myocytes is an important factor in stimulating myocyte growth by Ang II.
MESH: *Angiotensin-II-pharmacology; *Myocardium-cytology
MESH: Aging-physiology; Animals,-Newborn-growth-and-development; Animals,-Newborn-physiology; Biphenyl-Compounds-pharmacology; Cell-Division-drug-effects; Culture-Media,-Conditioned-pharmacology; Dose-Response-Relationship,-Drug; Fibroblasts-cytology; Fibroblasts-metabolism; Fibroblasts-physiology; Imidazoles-pharmacology; Losartan-; Rats-; Rats,-Wistar; Receptors,-Angiotensin-antagonists-and-inhibitors; Tetrazoles-pharmacology; Time-Factors
TG: Animal; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: physiology; pharmacology; growth-and-development; drug-effects; cytology; metabolism; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 0; 11128-99-7; 114798-26-4
NM: Biphenyl-Compounds; Culture-Media,-Conditioned; Imidazoles; Receptors,-Angiotensin; Tetrazoles; Angiotensin-II; Losartan
CN: HL27838HLNHLBI; HL47794HLNHLBI
SB: Index-Medicus
UD: 20001218
AN: 97405938
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 57 of 65 - MEDLINE (R) 1997 Part B
TI: Angiotensin II stimulates expression of the chemokine RANTES in rat glomerular endothelial cells. Role of the angiotensin type 2 receptor.
AU: Wolf,-G; Ziyadeh,-F-N; Thaiss,-F; Tomaszewski,-J; Caron,-R-J; Wenzel,-U; Zahner,-G; Helmchen,-U; Stahl,-R-A
AD: Department of Medicine, University of Hamburg, D-20246 Hamburg, Germany.
SO: J-Clin-Invest. 1997 Sep 1; 100(5): 1047-58
IS: 0021-9738
PY: 1997
LA: English
CP: UNITED-STATES
AB: Glomerular influx of monocytes/macrophages (M/M) occurs in many immune- and non-immune-mediated renal diseases. The mechanisms targeting M/M into the glomerulus are incompletely understood, but may involve stimulated expression of chemokines. We investigated whether angiotensin II (ANG II) induces the chemokine RANTES in cultured glomerular endothelial cells of the rat and in vivo. ANG II stimulated mRNA and protein expression of RANTES in cultured glomerular endothelial cells. The ANG II-induced RANTES protein was chemotactic for human monocytes. Surprisingly, the ANG II-stimulated RANTES expression was transduced by AT2 receptors because the AT2 receptor antagonists PD 123177 and CGP-42112A, but not an AT1 receptor blocker, abolished the induced RANTES synthesis. Intraperitoneal infusion of ANG II (500 ng/h) into naive rats for 4 d significantly stimulated glomerular RANTES mRNA and protein expression compared with solvent-infused controls. Immunohistochemistry revealed induction of RANTES protein mainly in glomerular endothelial cells and small capillaries. Moreover, ANG II- infused animals exhibited an increase in glomerular ED-1- positive cells compared with controls. Oral treatment with PD 123177 (50 mg/liter drinking water) attenuated the glomerular M/M influx without normalizing the slightly elevated systolic blood pressure caused by ANG II infusion, suggesting that the effects on blood pressure and RANTES induction can be separated. We conclude that the vasoactive peptide ANG II may play an important role in glomerular chemotaxis of M/M through local induction of the chemokine RANTES. The observation that the ANG II- mediated induction of RANTES is transduced by AT2 receptors may influence the decision as to which substances might be used for the therapeutic interference with the activity of the renin-angiotensin system.
MESH: *Angiotensin-II-pharmacology; *Kidney-Glomerulus-metabolism; *RANTES-biosynthesis; *Receptors,-Angiotensin-physiology
MESH: Cells,-Cultured; Endothelium-metabolism; Kidney-Glomerulus-drug-effects; Rats-; Rats,-Sprague-Dawley; Receptors,-Angiotensin-classification
TG: Animal; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: pharmacology; metabolism; drug-effects; biosynthesis; classification; physiology
RN: 0; 0; 11128-99-7
NM: RANTES; Receptors,-Angiotensin; Angiotensin-II
CN: DK07006DKNIDDK; DK44513DKNIDDK; DK45191DKNIDDK
SB: Abridged-Index-Medicus; Index-Medicus
UD: 20001218
AN: 97426466
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 58 of 65 - MEDLINE (R) 1997 Part B
TI: p53 Induces myocyte apoptosis via the activation of the renin-angiotensin system.
AU: Pierzchalski,-P; Reiss,-K; Cheng,-W; Cirielli,-C; Kajstura,-J; Nitahara,-J-A; Rizk,-M; Capogrossi,-M-C; Anversa,-P
AD: Department of Medicine, New York Medical College, Valhalla 10595, USA.
SO: Exp-Cell-Res. 1997 Jul 10; 234(1): 57-65
IS: 0014-4827
PY: 1997
LA: English
CP: UNITED-STATES
AB: The mechanism by which p53 activates apoptosis in various cell systems is unknown. In the absence of an external death stimulus, p53 and p53-dependent genes, bcl-2 and bax, cannot trigger apoptosis. However, p53 may enhance not only transcription of bax and repress bcl-2, but also may upregulate the local renin-angiotensin system, inducing the formation and secretion of angiotensin II from the cells. To test this hypothesis, adult rat ventricular myocytes were infected with AdCMV.p53, which resulted in downregulation of Bcl-2, upregulation of Bax, and death of 34% of the cells. Gel retardation assays demonstrated p53 binding in the promoters of angiotensinogen and angiotensin II AT1 receptor subtype. Angiotensinogen and AT1 mRNAs increased in AdCMV.p53 cells and this phenomenon was associated with a 14-fold increase in the secretion of angiotensin II. The AT1 receptor blocker losartan and angiotensin II antibody prevented p53-induced apoptosis. Thus, p53 enhances the myocyte renin-angiotensin-system and decreases the Bcl-2/Bax ratio in the cells, triggering apoptosis. The identification of this new pathway in p53-mediated apoptosis may be critical in the alterations of myocardial function in the pathologic heart.
MESH: *Angiotensin-II-physiology; *Apoptosis-physiology; *Muscle-Fibers-cytology; *Protein-p53-genetics; *Renin-physiology
MESH: Adenoviridae-; Angiotensinogen-metabolism; Gene-Expression-physiology; Gene-Transfer-Techniques; Heart-Ventricle-chemistry; Heart-Ventricle-cytology; Molecular-Sequence-Data; Muscle-Fibers-chemistry; Myocardium-chemistry; Myocardium-cytology; Promoter-Regions-Genetics-physiology; Proto-Oncogene-Proteins-genetics; Proto-Oncogene-Proteins-c-bcl-2-genetics; RNA,-Messenger-analysis; Rats-; Rats,-Sprague-Dawley; Receptors,-Angiotensin-genetics; Receptors,-Angiotensin-metabolism
TG: Animal; Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: physiology; metabolism; chemistry; cytology; genetics; analysis
RN: 0; 0; 0; 0; 0; 0; 11002-13-4; 11128-99-7; EC 3.4.23.15
NM: Bax-protein; Protein-p53; Proto-Oncogene-Proteins; Proto-Oncogene-Proteins-c-bcl-2; RNA,-Messenger; Receptors,-Angiotensin; Angiotensinogen; Angiotensin-II; Renin
SI: GENBANK/M12113; GENBANK/M31673; GENBANK/M74054; GENBANK/S66402; GENBANK/U17193
CN: HL38132HLNHLBI; HL39902HLNHLBI; HL40561HLNHLBI
SB: Index-Medicus
UD: 20001218
AN: 97366540
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 59 of 65 - MEDLINE (R) 1997 Part A
TI: Angiotensin II-mediated growth and antigrowth effects in cultured neonatal rat cardiac myocytes and fibroblasts.
AU: van-Kesteren,-C-A; van-Heugten,-H-A; Lamers,-J-M; Saxena,-P-R; Schalekamp,-M-A; Danser,-A-H
AD: Department of Pharmacology, Cardiovascular Research Institute COEUR, Erasmus University Rotterdam, Rotterdam, The Netherlands.
SO: J-Mol-Cell-Cardiol. 1997 Aug; 29(8): 2147-57
IS: 0022-2828
PY: 1997
LA: English
CP: ENGLAND
AB: Angiotensin II (Ang II) stimulates cardiovascular growth and remodeling via AT1 receptors. Recent experiments have shown that Ang II may also exert antiproliferative effects via AT2 receptors. We studied the effects of Ang II on protein and DNA content and synthesis rate in unstimulated and endothelin-1 (ET-1)-stimulated neonatal rat cardiomyocytes and fibroblasts, isolated from 1-3-day-old Wistar strain pups. Total protein and total DNA, as well as [3H]leucine and [3H]thymidine incorporation were measured following incubation with either vehicle, Ang II, ET-1 or Ang II+ET-1, both in the presence or absence of the AT1 receptor blocker losartan or the AT2 receptor blocker PD123319. In myocytes, ET-1 increased total protein (+38% relative to control) as well as [3H]leucine (+66%) and [3H]thymidine (+77%) incorporation. Ang II did not affect any of these parameters, nor did it influence the ET-1-induced responses. However, in the presence of PD123319 Ang II stimulated [3H]leucine (+24%) and [3H]thymidine (+30%) incorporation. In fibroblasts, ET-1 and Ang II did not significantly affect total DNA and [3H]thymidine incorporation. Ang II tended to increase total protein in these cells, an effect which was significant only in the presence of PD123319 (+17%). Ang II stimulated [3H]leucine incorporation (+24%) in fibroblasts. This effect was absent with losartan and enhanced in the presence of PD123319. These data demonstrate that AT1 receptor-mediated proliferative effects of Ang II in neonatal cardiac cells may become apparent only when its AT2 receptor-mediated antigrowth effects are blocked. The net growth effect of Ang II therefore depends on the cellular AT1/AT2 receptor ratio. Ang II does not appear to interfere with ET-1-induced effects.
MESH: *Angiotensin-II-pharmacology; *Fibroblasts-drug-effects; *Growth-Inhibitors-pharmacology; *Growth-Substances-pharmacology; *Heart-drug-effects; *Myocardium-metabolism
MESH: Animals,-Newborn; Cells,-Cultured; Endothelin-1-pharmacology; Fibroblasts-metabolism; Imidazoles-pharmacology; Inositol-Phosphates-metabolism; Losartan-pharmacology; Pyridines-pharmacology; Rats-; Rats,-Wistar; Receptors,-Angiotensin-antagonists-and-inhibitors; Receptors,-Angiotensin-physiology
TG: Animal
PT: Journal-Article
SH: pharmacology; drug-effects; metabolism; antagonists-and-inhibitors; physiology
RN: 0; 0; 0; 0; 0; 0; 0; 11128-99-7; 114798-26-4; 130663-39-7
NM: Endothelin-1; Growth-Inhibitors; Growth-Substances; Imidazoles; Inositol-Phosphates; Pyridines; Receptors,-Angiotensin; Angiotensin-II; Losartan; PD-123319
SB: Index-Medicus
UD: 20001218
AN: 97428629
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 60 of 65 - MEDLINE (R) 1997 Part A
TI: Candesartan cilexetil: a review of its preclinical pharmacology.
AU: Nishikawa,-K; Naka,-T; Chatani,-F; Yoshimura,-Y
AD: Pharmaceutical Research Division, Takeda Chemical Industries, Osaka, Japan.
SO: J-Hum-Hypertens. 1997 Sep; 11 Suppl 2S9-17
IS: 0950-9240
PY: 1997
LA: English
CP: ENGLAND
AB: Candesartan is a highly potent, long-acting and selective angiotensin II type 1 (AT1) receptor blocker. It is administered orally as the inactive prodrug candesartan cilexetil which is rapidly and completely converted to candesartan during gastrointestinal absorption. In vitro studies have shown that candesartan acts as an insurmountable angiotensin II receptor antagonist, binding tightly to and dissociating slowly from the AT1 receptor. The above characteristics are thought to contribute to the marked and long-lasting antihypertensive effects of candesartan cilexetil in several animal models of hypertension. These included rodent models of renal hypertension in which candesartan cilexetil also demonstrated efficacy equivalent to or greater than enalapril. In other animal models, candesartan cilexetil reduced the incidence of stroke, renal dysfunction and renal disease while reducing cardiac and vascular hypertrophy. Furthermore, candesartan cilexetil conferred some protection against cerebral and renal damage at a dose that had no blood pressure-lowering effect. In toxicity and general pharmacology studies, candesartan cilexetil was shown to possess a 'clean' profile with a large safety margin. Also it did not potentiate chemical- or autocoid-induced cough or anaphylactoid reactions.
MESH: *Antihypertensive-Agents-pharmacology; *Benzimidazoles-pharmacology; *Biphenyl-Compounds-pharmacology; *Receptors,-Angiotensin-antagonists-and-inhibitors
MESH: Benzimidazoles-pharmacokinetics; Benzimidazoles-toxicity; Biphenyl-Compounds-pharmacokinetics; Biphenyl-Compounds-toxicity; Hemodynamics-drug-effects
TG: Animal; Human
PT: Journal-Article; Review; Review,-Tutorial
SH: pharmacology; pharmacokinetics; toxicity; drug-effects; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 145040-37-5
NM: Antihypertensive-Agents; Benzimidazoles; Biphenyl-Compounds; Receptors,-Angiotensin; TCV-116
SB: Index-Medicus
UD: 20001218
AN: 97470539
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 61 of 65 - MEDLINE (R) 1997 Part A
TI: Pharmacokinetics of candesartan after single and repeated doses of candesartan cilexetil in young and elderly healthy volunteers.
AU: Hubner,-R; Hogemann,-A-M; Sunzel,-M; Riddell,-J-G
AD: Takeda Euro R&D Centre, Frankfurt/Main, Germany.
SO: J-Hum-Hypertens. 1997 Sep; 11 Suppl 2S19-25
IS: 0950-9240
PY: 1997
LA: English
CP: ENGLAND
AB: Candesartan cilexetil is rapidly and completely hydrolysed to the active compound candesartan during absorption from the gastrointestinal tract. Candesartan is a potent, long-acting, selective angiotensin II AT1 receptor blocker. The pharmacokinetics of candesartan were investigated after single and repeated once-daily doses of candesartan cilexetil in the dose range 2-16 mg in both younger (19-40 years) and elderly (65-78 years) healthy volunteers in five studies. Blood pressure, heart rate, and hormones associated with the renin-angiotensin system, and safety of candesartan cilexetil administration were also assessed. Placebo comparisons were made in four studies. Frequent blood samples were collected after the first single dose of candesartan cilexetil, and during the last dosing interval after 1 week repeated once-daily administration. Serum and plasma were analysed for candesartan cilexetil, candesartan and its inactive metabolite, CV-15959, as well as angiotensin I and II, aldosterone, plasma renin activity (PRA) and angiotensin-converting enzyme (ACE) activity. The AUC and Cmax of candesartan showed dose-proportional increases in the dose range of 2-16 mg candesartan cilexetil after both single and repeated once-daily tablet intake, indicating linear pharmacokinetics in both younger and elderly healthy subjects. The pharmacokinetics did not change on repeated dosing and, as expected from the half-life of candesartan of approximately 9 h in younger subjects, there was almost no accumulation after repeated once-daily dosing. The time to peak candesartan concentrations after tablet intake was consistently approximately 4 h at all dose levels. Both Cmax and AUC of candesartan were increased after single and repeated once-daily dosing in the elderly compared to younger subjects by approximately 50%. However, no accumulation after repeated once-daily dosing were seen in the elderly. The half-life of candesartan in the elderly (9-12 h) was somewhat longer than in the younger healthy adult volunteers (approximately 9 h) and no gender-related differences in the disposition of candesartan were observed. Serum concentrations of CV-15959 were much lower than candesartan, and reached peak serum concentrations later, about 4-9 h after dose intake. The elimination of CV-15959 was somewhat slower than that of candesartan. Candesartan cilexetil, the prodrug to candesartan, was not measurable in serum. No differences in ACE activity or serum aldosterone concentrations were observed between subjects receiving candesartan cilexetil and placebo tablets. Plasma angiotensin I and II concentrations and PRA were augmented after single doses and further increased after 1 week repeated candesartan cilexetil dosing. Single and repeated doses of candesartan cilexetil were well tolerated in the younger and elderly volunteers. Only mild adverse events were recorded, with 'headache' as the most commonly reported event, and no increase in the number of reported adverse events was observed with higher doses of candesartan cilexetil. No clinically significant changes in respect to vital signs, physical examination, ECG, and clinical laboratory tests were observed.
MESH: *Antihypertensive-Agents-pharmacokinetics; *Benzimidazoles-pharmacokinetics; *Biphenyl-Compounds-pharmacokinetics; *Receptors,-Angiotensin-antagonists-and-inhibitors
MESH: Adult-; Age-Factors; Aged-; Angiotensin-II-blood; Benzimidazoles-administration-and-dosage; Benzimidazoles-pharmacology; Biphenyl-Compounds-administration-and-dosage; Biphenyl-Compounds-pharmacology; Cross-Over-Studies; Double-Blind-Method
TG: Female; Human; Male
PT: Clinical-Trial; Journal-Article; Randomized-Controlled-Trial
SH: blood; pharmacokinetics; administration-and-dosage; pharmacology; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 11128-99-7; 145040-37-5
NM: Antihypertensive-Agents; Benzimidazoles; Biphenyl-Compounds; Receptors,-Angiotensin; Angiotensin-II; TCV-116
SB: Index-Medicus
UD: 20001218
AN: 97470540
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 62 of 65 - MEDLINE (R) 1997 Part A
TI: Functional evidence that the central renin-angiotensin system plays a role in the pressor response induced by central injection of carbachol.
AU: Saad,-W-A; Luiz,-A-C; Camargo,-L-A; Silveira,-J-E; Foglia,-S; Menani,-J-V; Saad,-W-A
AD: Departamento de Ciencias Fisiologicas, Faculdade de Odontologia, Universidade Estadual Paulista, Araraquara, SP, Brasil.
SO: Braz-J-Med-Biol-Res. 1997 Apr; 30(4): 493-6
IS: 0100-879X
PY: 1997
LA: English
CP: BRAZIL
AB: We investigated the effects of losartan, an AT1-receptor blocker, and ramipril, a converting enzyme inhibitor, on the pressor response induced by angiotensin II (ANG II) and carbachol (a cholinergic receptor agonist). Male Holtzman rats (250-300 g) with a stainless steel cannula implanted into the lateral ventricle (LV) were used. The injection of losartan (50 nmol/1 microliter) into the LV blocked the pressor response induced by ANG II (12 ng/1 microliter) and carbachol (2 nmol/1 microliter). After injection of ANG II and carbachol into the LV, mean arterial pressure (MAP) increased to 31 +/- 1 and 28 +/- 2 mmHg, respectively. Previous injection of losartan abolished the increase in MAP induced by ANG II and carbachol into the LV (2 +/- 1 and 5 +/- 2 mmHg, respectively). The injection of ramipril (12 ng/1 microliter) prior to carbachol blocked the pressor effect of carbachol to 7 +/- 3 mmHg. These results suggest an interaction between central cholinergic pathways and the angiotensinergic system in the regulation of arterial blood pressure.
MESH: *Angiotensin-Converting-Enzyme-Inhibitors-pharmacology; *Blood-Pressure-drug-effects; *Carbachol-pharmacology; *Cerebral-Ventricles-drug-effects; *Cholinergic-Agonists-pharmacology; *Losartan-pharmacology; *Pressoreceptors-drug-effects; *Ramipril-pharmacology; *Receptors,-Angiotensin-antagonists-and-inhibitors; *Renin-Angiotensin-System-physiology
MESH: Rats-; Rats,-Sprague-Dawley
TG: Animal; Male; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: pharmacology; drug-effects; antagonists-and-inhibitors; physiology
RN: 0; 0; 0; 114798-26-4; 51-83-2; 87333-19-5
NM: Angiotensin-Converting-Enzyme-Inhibitors; Cholinergic-Agonists; Receptors,-Angiotensin; Losartan; Carbachol; Ramipril
SB: Index-Medicus
UD: 20001218
AN: 97395666
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 63 of 65 - MEDLINE (R) 1997 Part A
TI: Transforming growth factor beta 1 and renal injury following subtotal nephrectomy in the rat: role of the renin-angiotensin system.
AU: Wu,-L-L; Cox,-A; Roe,-C-J; Dziadek,-M; Cooper,-M-E; Gilbert,-R-E
AD: Department of Medicine, Austin and Repatriation Medical Centre, Victoria, Australia.
SO: Kidney-Int. 1997 May; 51(5): 1553-67
IS: 0085-2538
PY: 1997
LA: English
CP: UNITED-STATES
AB: Transforming growth factor-beta (TGF-beta) and the renin-angiotensin system (RAS) have both been implicated in the pathogenesis of chronic renal disease. The present experiment investigated the chronology of TGF-beta 1 gene expression following subtotal nephrectomy (STNx) in the rat and the effect of blocking the RAS by angiotensin converting enzyme (ACE) inhibition or by angiotensin II receptor (AT1) antagonism. Rats that had undergone subtotal nephrectomy developed hypertension, proteinuria, renal impairement, glomerulosclerosis, tubulointerstitial fibrosis and mononuclear cell infiltration. These changes were associated with a 2.5-fold increase in TGF-beta 1 gene expression during a 16-week time course. In situ hybridization localized TGF-beta 1 mRNA to sclerotic glomeruli, areas of tubuloin-terstitial injury and sites of mononuclear cell infiltration. Administration of the ACE inhibitor ramipril and the AT1 receptor blocker valsartan blunted the increase in TGF-beta 1 mRNA, and attenuated the structural and functional manifestations of injury. These data suggest an interaction between the intrarenal RAS and TGF-beta in the pathogenesis of the glomerular and tubulointerstitial fibrosis that follow a major reduction in renal mass.
MESH: *Gene-Expression-Regulation; *Kidney-pathology; *Nephrectomy-; *Renin-Angiotensin-System-physiology; *Transforming-Growth-Factor-beta-genetics
MESH: Angiotensin-II-physiology; Blotting,-Northern; In-Situ-Hybridization; Rats-; Rats,-Sprague-Dawley
TG: Animal; Male; Support,-Non-U.S.-Gov't
PT: Journal-Article
SH: physiology; pathology; genetics
RN: 0; 11128-99-7
NM: Transforming-Growth-Factor-beta; Angiotensin-II
SB: Index-Medicus
UD: 20001218
AN: 97294800
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 64 of 65 - MEDLINE (R) 1997 Part A
TI: Angiotensin AT1 receptor inhibition. Effects on hypertrophic remodeling and ACE expression in rats with pressure-overload hypertrophy due to ascending aortic stenosis.
AU: Weinberg,-E-O; Lee,-M-A; Weigner,-M; Lindpaintner,-K; Bishop,-S-P; Benedict,-C-R; Ho,-K-K; Douglas,-P-S; Chafizadeh,-E; Lorell,-B-H
AD: Charles A. Dana Research Institute, Boston, Mass, USA.
SO: Circulation. 1997 Mar 18; 95(6): 1592-600
IS: 0009-7322
PY: 1997
LA: English
CP: UNITED-STATES
AB: BACKGROUND: We tested the hypothesis that long-term administration of the specific angiotensin II subtype 1 (AT1)-receptor blocker BMS-186295 will regress hypertrophy and modify left ventricular angiotensin converting enzyme (ACE) expression in rats with ascending aortic stenosis. METHODS AND RESULTS: Six weeks after surgery, rats with ascending aortic stenosis were randomized to receive either the AT1-receptor blocker BMS-186295 50 mg.kg-1.d-1 (n = 49), amlodipine 2.5 mg.kg-1.d-1 (n = 48) as a positive control for systemic vasodilation, or no drug (n = 48) and compared with sham-operated rats (n = 39). Drug treatment was continued for 15 weeks. Left ventricular ACE mRNA levels were measured by ribonuclease protection assay. The left ventricular/body weight ratio was increased 43% in hearts from rats with untreated left ventricular hypertrophy (LVH) versus control hearts (P < ..05). However, there was no difference in either the left ventricular/body weight ratio (2.78 +/- 0.08 versus 2.81 +/- 0.20 mg/g; P = NS) or myocyte cross-sectional area in the AT1-blocker-treated versus untreated LVH hearts. Amlodipine also showed no effect on regression of hypertrophy. In vivo left ventricular systolic pressure was significantly higher in untreated LVH versus sham-operated rats (193 +/- 8 versus 118 +/- 4 mm Hg; P < .05), and there was a similar severe elevation of left ventricular systolic pressure in the AT1-blocker- and amlodipine-treated LVH groups (189 +/- 9 and 188 +/- 16 mm Hg; P = NS versus untreated LVH). In vivo left ventricular end-diastolic pressure was higher in the untreated LVH than in the sham-operated rats (14.8 +/- 2.3 versus 7.0 +/- 0.5 mm Hg; P < .05). Left ventricular end-diastolic pressure was lower in the AT1-blocker-treated (11.0 +/- 1.7 mm Hg) and amlodipine-treated rats (11.5 +/- 1.8 mm Hg) and was similar to left ventricular end-diastolic pressure in the sham-operated rats (P = NS). Left ventricular ACE mRNA levels were elevated in untreated LVH rats but were normalized in both the AT1-blocker-treated rats and amlodipine-treated rats. CONCLUSIONS: Long-term AT1-receptor blockade did not regress LVH in rats with persistent systolic pressure overload due to ascending aortic stenosis. However, both AT1-receptor blockade and amlodipine improved in vivo left ventricular end-diastolic pressure in association with the normalization of left ventricular ACE mRNA levels.
MESH: *Aortic-Valve-Stenosis-complications; *Hypertension-complications; *Hypertrophy,-Left-Ventricular-etiology; *Hypertrophy,-Left-Ventricular-metabolism; *Peptidyl-Dipeptidase-A-metabolism; *Receptors,-Angiotensin-antagonists-and-inhibitors
MESH: Antihypertensive-Agents-pharmacology; Aorta-; Biphenyl-Compounds-pharmacology; Echocardiography-; Hypertrophy,-Left-Ventricular-diagnosis; Myocardium-pathology; Norepinephrine-blood; Rats-; Renin-blood; Tetrazoles-pharmacology; Ventricular-Function
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: Journal-Article
SH: pharmacology; complications; diagnosis; etiology; metabolism; pathology; blood; antagonists-and-inhibitors
RN: 0; 0; 0; 0; 138402-11-6; 51-41-2; EC 3.4.15.1; EC 3.4.23.15
NM: Antihypertensive-Agents; Biphenyl-Compounds; Receptors,-Angiotensin; Tetrazoles; irbesartan; Norepinephrine; Peptidyl-Dipeptidase-A; Renin
CN: HL5286401HLNHLBI
SB: Abridged-Index-Medicus; Index-Medicus
UD: 20001218
AN: 97234032
XREC: ABSTRACT (AB)
--------------------------------------------------------------------------------
Record 65 of 65 - MEDLINE (R) 1997 Part A
TI: Prevention of diabetic nephropathy.
AU: Materson,-B-J; Preston,-R-A
AD: University of Miami, USA.
SO: Hosp-Pract-(Off-Ed). 1997 Feb 15; 32(2): 129-34, 139-40
IS: 8750-2836
PY: 1997
LA: English
CP: UNITED-STATES
AB: Normalization of blood pressure--and use of an ACE inhibitor or AT1-receptor blocker for patients with abnormal albumin or creatinine levels--can prevent or significantly slow the rate of progression toward end-stage renal disease.
MESH: *Angiotensin-Converting-Enzyme-Inhibitors-therapeutic-use; *Diabetic-Nephropathies-physiopathology; *Diabetic-Nephropathies-prevention-and-control; *Kidney-Failure,-Chronic-prevention-and-control
MESH: Enalapril-therapeutic-use; Hypertension-complications; Hypertension-drug-therapy; Hypertension-prevention-and-control; Kidney-Failure,-Chronic-etiology
TG: Human
PT: Journal-Article; Review; Review,-Tutorial
SH: therapeutic-use; physiopathology; prevention-and-control; complications; drug-therapy; etiology
RN: 0; 75847-73-3
NM: Angiotensin-Converting-Enzyme-Inhibitors; Enalapril
SB: Abridged-Index-Medicus; Index-Medicus
UD: 20001218
AN: 97192833
XREC: ABSTRACT (AB)