Document Detail


Role of kinins and nitric oxide in the antihypertrophic effect of ramipril.
MedLine Citation:
PMID:  7515854     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We examined the effect of non-antihypertensive doses of the angiotensin-converting enzyme inhibitor ramipril, kinins, and/or nitric oxide on left ventricular hypertrophy in rats with aortic coarctation. We investigated the effect of either HOE 140, a specific B2 receptor antagonist, or NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, on the antihypertrophic effect of ramipril at non-antihypertensive doses (10 micrograms/kg per day) failed to alter left ventricular hypertrophy significantly, although a small decrease was obtained. Given at a dose of 1 mg/kg per day for 6 weeks, ramipril prevented increased blood pressure and left ventricular hypertrophy after aortic coarctation. Neither of these effects was blocked by simultaneous administration of HOE 140 (500 micrograms/kg per day). In rats with aortic coarctation treated with L-NAME, blood pressure increased further but left ventricular weight did not. Ramipril (1 mg/kg per day) significantly reduced left ventricular hypertrophy, although blood pressure was still higher than in rats given water alone. The slope of the correlation between left ventricular weight and blood pressure in rats that received L-NAME was significantly lower than in rats that did not (0.52 versus 1.29; P = .008). This suggests that for each 1 mm Hg that the blood pressure increased, the increase in left ventricular weight was less in the L-NAME groups. Thus, only antihypertensive doses of ramipril possessed antihypertrophic activity. Kinins did not participate in the chronic antihypertensive and antihypertrophic effects of ramipril. In hypertension induced or aggravated by chronic nitric oxide synthase, L-NAME partially impaired development of left ventricular hypertrophy for reasons that are unclear.
Authors:
N E Rhaleb; X P Yang; A G Scicli; O A Carretero
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Hypertension     Volume:  23     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1994 Jun 
Date Detail:
Created Date:  1994-07-11     Completed Date:  1994-07-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  865-8     Citation Subset:  IM    
Affiliation:
Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI 48202-2689.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Oxidoreductases / antagonists & inhibitors
Animals
Aortic Coarctation / complications
Arginine / analogs & derivatives,  pharmacology
Blood Pressure / drug effects
Cardiomegaly / etiology,  prevention & control*
Dose-Response Relationship, Drug
Heart Ventricles
Hypertension / etiology
Kinins / physiology*
Male
Myocardium / pathology
NG-Nitroarginine Methyl Ester
Nitric Oxide / physiology*
Nitric Oxide Synthase
Organ Size / drug effects
Ramipril / pharmacology*
Rats
Grant Support
ID/Acronym/Agency:
HL-28982-12/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Kinins; 10102-43-9/Nitric Oxide; 50903-99-6/NG-Nitroarginine Methyl Ester; 74-79-3/Arginine; 87333-19-5/Ramipril; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.4.-/Amino Acid Oxidoreductases

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