CONTRIBUTION OF BRADYKININ TO THE CARDIOVASCULAR EFFECTS OF RAMIPRIL

From pharmacologic investigations and clinical studies it is known tha t angiotensin-converting enzyme (ACE) inhibitors exhibit additional lo cal actions, which are not related to hemodynamic changes and which ca nnot be explained simply by interference with the renin-angiotensin sy stem with subsequent inhibition of angiotensin II formation. Because A CE is identical to kininase II, which inactivates the nonapeptide brad ykinin (BK), potentiation of BK might be responsible for these additio nal effects of ACE inhibitors. To prove the specificity of BK-mediated effects by ACE inhibition, we used the specific B, kinin receptor ant agonist HOE 140 in different models: endothelial cell cultures; athero sclerosis in high-cholesterol-fed rabbits; neointima formation with sm ooth cell proliferation and migration after endothelial denudation in rats; myocardial ischemia in rats, rabbits, and dogs; and left ventric ular hypertrophy in rats. The beneficial effects of ramipril or BK giv en in non-blood pressure-lowering doses in these models were abolished by HOE 140 (icatibant). Ramipril exerts cardioprotective effects in d ifferent experimental models. The formation of the endothelial autacoi ds nitric oxide and prostacyclin, enhanced when BK degradation is inhi bited by ACE inhibition, may contribute to the observed beneficial eff ects.