'R investigate the influence of local cardiac converting enzyme (CE) inhibition on the effects of angiotensin I (ANG I). ANG 11, and hradykinin (BK), experiments were performed in ischemic isolated perfused working rat hearts. Acute regional myocardial ischemia was induced by 15 min occlusion of the left coronary artery followed by reperfusion. In ischemic isolated rat hearts, perfusion with ramiprilat 1100 ng/ml, 2.58 x 10-7 mold/1). the active moiety of the CE inhibitor ramipril, after coronary occlusion protected against ventricular fibrillation that invariably occurred in untreated control hearts in the reperfusion period. Addition of ANG I and ANG II to the perfusate enhanced, whereas BK reduced postischemic reperfusion arrhythmias, which were al-most abolished in the hearts from ramipril (1 mg/kg p.o.) pretreated rats. Perfusion with ANG I and ANG II reduced cardiac function and coronary flow, increased the activities of lactate dehydrogenase and creatine kinase in the perfusate, and decreased high-energy-rich phosphates and glycogen in the myocardium. In contrast, BK reduced the enzymatic activities in the perfusate and improved the metabolic parameters in the myocardium. In hearts from ramipril pretreated animals, the ANG I effects were abolished, whereas the ANG II actions remained unchanged. The results of these experiments are consistent with the hypothesis that the beneficial effects of CE inhibitors on ventricular arrhythmias, cardiac function, and metabolism are dtie to local interference with CE in the coronary vascular wall or heart tissue and subsequent reduction of local ANG 11 generation and BK degradation.
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