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 mug/kg/h or 300 mug/kg/h for 70 min, IV) was administered 20 min before ischemia with or without pretreatment with Nomega-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 27.62%, n = 7, respectively) compared with the control (46.54%, n = 10). The infarct size-reducing effect of quinaprilat was completely blocked by pretreatment with L-NAME (43.82%, n = 8) and 5-HD (50.13%, n = 8) and posttreatment with 5-HD (50.32%, 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.