ACE inhibitors induce an increase in kinin levels with subsequent release of nitric oxide (NO) and prostacyclin, as shown in cultured endothelial cells and isolated rat hearts. Isolated perfused working rat hearts continuously release kinins and prostacyclin. During ischemia after ligation of the left coronary artery kinin and prostacyclin concentrations in the venous effluent of the hearts are increased. ACE inhibition with ramiprilat increases kinin concentrations during normoxia, ischemia and reperfusion, whereas deendothelialization markedly reduces kinin and prostacyclin outflow in controls as well as in ACE inhibitor-treated hearts. Rat hearts with postischemic reperfusion arrhythmias are protected by ramiprilat- and bradykinin perfusion, cardiodynamics and metabolism of treated hearts are improved. These effects are observed in concentrations too low to increase coronary flow. The cardioprotective effects of ramiprilat and bradykinin are abolished by the specific B2-kinin receptor antagonist icatibant and by an inhibitor of NO-synthase. Long-term treatment (20 weeks) with ramipril in a blood-pressure-lowering dose (1 mg/kg/day) and a subantihypertensive dose (10 micromg/kg/day) protects spontaneously hypertensive rats (stroke prone) against hypertension and left ventricular hypertrophy in the high dose. In addition, both treatment regimens induce myocardial capillary growth. Isolated hearts of these animals show increased myocardial contractility and coronary flow, reduced release of cytosolic enzymes into the coronary effluent, and improved myocardial metabolism. These changes are observed even at a dose of ramipril which does not affect blood pressure and left ventricular hypertrophy. They are abolished by chronic blockade of kinin receptors with icatibant.(ABSTRACT TRUNCATED AT 250 WORDS)