Inhibition of angiotensin-converting enzyme increases the nitric oxide levels in canine ischemic myocardium

Since angiotensin-converting enzyme (ACE) produces angiotensin II in the he art, ACE inhibitors may prevent coronary vasoconstriction and increase coro nary blood flow On the other hand, since ACE inhibitors also inhibit kinina se LI which results in reduced degradation of bradykinin, ACE inhibitors ma y increase cardiac nitric oxide (NO) levels via stimulation of bradykinin r eceptors. This study was undertaken to test whether ACE inhibitors increase the cardiac NO levels and coronary blood now in the ischemic myocardium. I n 34 open-chest dogs, the left anterior descending coronary artery was perf used through an extracorporeal bypass tube from the left carotid artery Whe n either imidaprilat or cilazaprilat of 3 mu g/kg/min was infused into the bypass tube for 10 min after reduction of coronary blood flow due to partia l occlusion of the bypass tube, coronary blood flow increased from 31 +/- 1 to either 45 +/- 5 or 43 +/- 4 ml/100 g/min despite no changes in coronary perfusion pressure (43 +/- 2 mmHg). During an infusion of either imidapril at or cilazaprilat, bradykinin and the end-products of NO (nitrate + nitrit e) concentrations of coronary venous blood were markedly increased, which w ere attenuated by either HOE-140 tan inhibitor of bradykinin receptors) or by N-omega-nitro-L-arginine methyl ester tan inhibitor of NO synthase). We also observed increases in cardiac bradykinin and NO levels due to either i midaprilat or cilazaprilat in the low constant coronary blood flow conditio n. It is concluded that ACE inhibitors can increase cardiac NO levels via t he accumulation of bradykinin in the ischemic myocardium. (C) 1998 Academic Press.