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: Xuehai Chen, Shinya Minatoguchi, Ningyuan Wang, Masazumi Arai, Cuanjiang Lu, Yoshihiro Uno, Yu Misao, Genzou Takemura, Hisayoshi Fujiwara
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 41 Issue 6 Pg. 938-45 (Jun 2003) ISSN: 0160-2446 [Print] United States
• PMID: 12775974 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Anti-Arrhythmia Agents
• Decanoic Acids
• Hydroxy Acids
• Membrane Proteins
• Potassium Channel Blockers
• Potassium Channels
• Tetrahydroisoquinolines
• mitochondrial K(ATP) channel
• Nitric Oxide
• Hydroxyl Radical
• quinaprilat
• 5-hydroxydecanoic acid
• Nitric Oxide Synthase
• NG-Nitroarginine Methyl Ester

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Decanoic Acids (pharmacology)
• Heart Ventricles (metabolism, pathology)
• Hemodynamics
• Hydroxy Acids (pharmacology)
• Hydroxyl Radical (metabolism)
• Male
• Membrane Proteins (metabolism)
• Mitochondria, Heart (metabolism)
• Myocardial Infarction (etiology, pathology, prevention & control)
• Myocardial Reperfusion Injury (complications)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase (metabolism)
• Potassium Channel Blockers (pharmacology)
• Potassium Channels (metabolism)
• Rabbits
• Tetrahydroisoquinolines (pharmacology)