title: Quinaprilat reduces myocardial infarct size involving nitric oxide production and mitochondrial KATP channel in rabbits.
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.
authors.affiliation: Second Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Xuehai
authors.initials: X
authors.lastname: Chen
authors.forename: Shinya
authors.initials: S
authors.lastname: Minatoguchi
authors.forename: Ningyuan
authors.initials: N
authors.lastname: Wang
authors.forename: Masazumi
authors.initials: M
authors.lastname: Arai
authors.forename: Cuanjiang
authors.initials: C
authors.lastname: Lu
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uno
authors.forename: Yu
authors.initials: Y
authors.lastname: Misao
authors.forename: Genzou
authors.initials: G
authors.lastname: Takemura
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics; D006880:Hydroxy Acids / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D011817:Rabbits; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D008565:Membrane Proteins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D044005:Tetrahydroisoquinolines; C117780:mitochondrial K(ATP) channel; D009569:Nitric Oxide; D017665:Hydroxyl Radical; C054501:quinaprilat; C052853:5-hydroxydecanoic acid; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester