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Reduction of myocardial infarct size by tetrahydrobiopterin: possible involvement of mitochondrial KATP channels activation through nitric oxide production.

Abstract
This study examined whether intravenous administration of tetrahydrobiopterin (BH4) reduces myocardial infarct size following ischemia/reperfusion (I/R) in rats, and the mechanisms of its protective effect were also investigated. Rats were subjected to 30 minutes of ischemia by ligation of the left coronary artery and 2 hours of reperfusion. The infarct size was determined as a percentage of the area at risk by triphenyltetrazolium staining. Intravenous administration of BH4 (0.01 mg/kg-1 mg/kg) significantly reduced the myocardial infarct size. Nitrite plus nitrate (NOx) and cGMP levels in the hearts were significantly increased by the treatment with BH4, and the infarct size-limiting effect of BH4 was abolished by the co-administration of NG-nitro-L-arginine methyl ester, a specific inhibitor of nitric oxide synthase, or 5-hydroxydecanoic acid, a specific inhibitor of mitochondrial ATP-sensitive potassium channel (mitoKATP channel). These findings suggest that BH4 has a cardioprotective effect against I/R in vivo, and its protective effect appeared to be involved in the opening of mitoKATP channels through increased nitric oxide production.
AuthorsTeruaki Wajima, Shunichi Shimizu, Toshihito Hiroi, Masakazu Ishii, Yuji Kiuchi
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 47 Issue 2 Pg. 243-9 (Feb 2006) ISSN: 0160-2446 [Print] United States
PMID16495762 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Anti-Arrhythmia Agents
  • Decanoic Acids
  • Enzyme Inhibitors
  • Hydroxy Acids
  • Nitrates
  • Nitrites
  • Potassium Channels
  • mitochondrial K(ATP) channel
  • Biopterin
  • Nitric Oxide
  • Malondialdehyde
  • 5-hydroxydecanoic acid
  • Arginine
  • sapropterin
  • Cyclic GMP
  • NG-Nitroarginine Methyl Ester
Topics
  • Animals
  • Anti-Arrhythmia Agents (pharmacology)
  • Arginine (pharmacology)
  • Biopterin (administration & dosage, analogs & derivatives, metabolism, pharmacology)
  • Cyclic GMP (analysis)
  • Decanoic Acids (pharmacology)
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors (pharmacology)
  • Hydroxy Acids (pharmacology)
  • Male
  • Malondialdehyde (analysis)
  • Myocardial Infarction (drug therapy, etiology, pathology, physiopathology)
  • NG-Nitroarginine Methyl Ester (pharmacology)
  • Nitrates (analysis)
  • Nitric Oxide (biosynthesis)
  • Nitrites (analysis)
  • Potassium Channels (drug effects, metabolism)
  • Rats
  • Rats, Sprague-Dawley

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