Experimental evidence for effects of ramipril on cardiac and vascular hypertrophy beyond blood pressure reduction.
In renal hypertensive rats with pressure overload left ventricular hypertrophy the angiotensin converting enzyme inhibitor ramipril, given in a high blood pressure lowering dose as well as in a low, non-antihypertensive dose, prevented and regressed left ventricular hypertrophy. These beneficial effects were abolished by coadministration of the specific bradykinin receptor antagonist (HOE 140) in the prevention--but not in the regression studies. Vascular function of rats with pressure overload left ventricular hypertrophy was impaired, whereas treated animals showed a reversal to normal. The angiotensin II subtype AT1 receptor antagonist, losartan, was barely active in the prevention, however markedly active in the regression of left ventricular hypertrophy. From these experimental studies in rats with pressure overload left ventricular hypertrophy and vascular dysfunction we conclude that inhibition of bradykinin degradation induced by ramipril may contribute to the antihypertrophic action during the prevention phase, whereas attenuation of angiotensin II formation may be more important during the regression period. In another model, the spontaneously hypertensive rat (SHR and stroke prone SHR)--a non-renal hypertensive model--cardiac left ventricular hypertrophy could be reduced by chronic high-dose ramipril treatment in prevention and regression studies, whereas the low dose regimen only reduced left ventricular hypertrophy in the regression experiments. In addition, both doses improved the myocardial capillary supply to the heart leading to improved function and metabolism. In comparison, vascular hypertrophy of the mesenteric artery could only be prevented by early-onset high dose treatment with the angiotensin converting enzyme inhibitor but not once hypertrophy has been established.(ABSTRACT TRUNCATED AT 250 WORDS)
Linz
W
W
Department of Pharmacology, Hoechst AG, Frankfurt/Main, Germany.
Gohlke
P
P
Unger
T
T
Schölkens
B A
BA
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D004195:Disease Models, Animal; D004341:Drug Evaluation; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy* / Q000503:physiopathology; D017257:Ramipril / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR
D000959:Antihypertensive Agents; C065679:icatibant; D017257:Ramipril; D001920:Bradykinin