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

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

Xuehai Chen, Shinya Minatoguchi, Ningyuan Wang, Masazumi Arai, Cuanjiang Lu, Yoshihiro Uno, Yu Misao, Genzou Takemura, Hisayoshi Fujiwara

J Cardiovasc Pharmacol. 2003 Jun;41(6):938-45.

PMID: 12775974

Abstract:

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 microg/kg/h or 300 microg/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 27.6 +/- 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP71186533	5-Hydroxydecanoic acid sodium salt		71186-53-3	Price

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