Quinaprilat Reduces Myocardial Infarct Size Involving Nitric Oxide Production and Mitochondrial KATP Channel in Rabbits

This study examined whether quinaprilat, an angiotensin-converting enzyme inhibitor, reduces the infarct size, and investigated the mechanisms for its infarct size–reducing effect, in rabbits. Japanese white rabbits underwent 30 min of ischemia and 48 h of reperfusion. Quinaprilat (100 &mgr;g/kg/h or 300 &mgr;g/kg/h for 70 min, IV) was administered 20 min before ischemia with or without pretreatment with N ω-nitro-l-arginine methyl ester (l-NAME) (10 mg/kg, IV, a nitric oxide synthase inhibitor), 5-hydroxydecanoic acid sodium salt (5-HD) or posttreatment with 5-HD (5 mg/kg, IV, a mitochondrial KATP channel blocker). The area at risk as a percentage of the left ventricle was determined by Evans blue dye and the infarct size was determined as a percent of the area at risk by triphenyl tetrazolium chloride staining. Using a microdialysis technique, myocardial interstitial levels of 2,5-dihydroxybenzoic acid (2,5-DHBA), an indicator of hydroxyl radicals, and NOx, an indicator of nitric oxide, were measured before, during, and after 30 min of ischemia. Quinaprilat significantly reduced the infarct size in a dose-dependent manner (30.1 ± 3%, n = 10, and 27.6 ± 2%, n = 7, respectively) compared with the control (46.5 ± 4%, n = 10). The infarct size–reducing effect of quinaprilat was completely blocked by pretreatment with l-NAME (43.8 ± 2%, n = 8) and 5-HD (50.1 ± 3%, n = 8) and posttreatment with 5-HD (50.3 ± 2%, n = 8), respectively. Quinaprilat did not affect the myocardial interstitial 2,5-DHBA level but significantly increased the NOx level during ischemia and reperfusion. Quinaprilat reduces myocardial infarct size involving NO production and mitochondrial KATP channels in rabbits without collateral circulation.