EXPERIMENTAL-EVIDENCE FOR EFFECTS OF RAMIPRIL ON CARDIAC AND VASCULARHYPERTROPHY BEYOND BLOOD-PRESSURE REDUCTION

In renal hypertensive rats with pressure overload left ventricular hyp ertrophy the angiotensin converting enzyme inhibitor ramipril, given i n a high blood pressure lowering dose as well as in a low non-antihype rtensive dose, prevented and regressed left ventricular hypertrophy. T hese beneficial effects were abolished by coadministration of the spec ific 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 a nimals showed a reversal to normal. The angiotensin II subtype AT(1) r eceptor antagonist, losartan, was barely active in the prevention, how ever 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 inhi bition of bradykinin degradation induced by ramipril may contribute to the antihypertrophic action during the prevention phase, whereas atte nuation of angiotensin II formation may be more important during the r egression period. In another model, the spontaneously hypertensive rat (SHR and stroke prone SHR) - a non-renal hypertensive model cardiac l eft ventricular hypertrophy could be reduced by chronic high-dose rami pril treatment in prevention and regression studies, whereas the low d ose regimen only reduced left ventricular hypertrophy in the regressio n experiments. In addition, both doses improved the myocardial capilla ry 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 c onverting enzyme inhibitor but not once hypertrophy has been establish ed. However, the angiotensin converting enzyme inhibitor improved vasc ular function under all treatment conditions independently of its effe ct on blood pressure or on vascular hypertrophy. Conclusion: the obser ved cardiovascular beneficial actions of ramipril independently of its effect on blood pressure in renal hypertensive rats and SHR may have been the result of a local accumulation of bradykinin beside the decre ase in the formation of angiotensin II.