Resveratrol protects myocardial ischemia-reperfusion injury through both NO-dependent and NO-independent mechanisms

Free Radic Biol Med. 2004 Mar 15;36(6):774-81. doi: 10.1016/j.freeradbiomed.2003.12.016.


We previously showed that resveratrol (3,4',5-trihydroxystilbene) stimulates NO production and is cardioprotective in rat heart subjected to ischemia-reperfusion (I/R rat heart). We now show that in I/R rat heart, inducible nitric oxide synthase (iNOS) expression is markedly induced, while expression of endothelial nitric oxide synthase (eNOS) and nueronal nitric oxide synthase (nNOS) is unchanged. In animals preconditioned with resveratrol (0.5 to 1 mg/kg body wt), I/R-induced iNOS induction is abrogated; however, expression of eNOS and nNOS is greatly upregulated. The protective effects of resveratrol on I/R rat heart include reduced rhythm disturbances, reduced cardiac infarct size, and decreased plasma levels of lactate dehydrogenase (LDH) and creatine kinase (CK). Among these, the reductions in LDH/CK levels and infarct size are NO-dependent as the coadministration of N(omega)-nitro-L-arginine methyl ester (L-NAME, 1 mg/kg body wt) with resveratrol abolishes the resveratrol effect. In contrast, the reductions in the severity of ventricular arrhythmia and mortality rate are not affected by L-NAME coadministration, suggesting that a NO-independent mechanism is involved.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / metabolism
  • Blood Pressure / drug effects
  • Coronary Disease / drug therapy
  • Coronary Disease / metabolism
  • Creatine Kinase / blood
  • Creatine Kinase / metabolism
  • Gene Expression / drug effects
  • Heart Rate / drug effects
  • L-Lactate Dehydrogenase / blood
  • L-Lactate Dehydrogenase / metabolism
  • Models, Animal
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / metabolism
  • Myocardial Reperfusion Injury / metabolism
  • Myocardial Reperfusion Injury / prevention & control*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / biosynthesis*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol
  • Stilbenes / metabolism
  • Stilbenes / pharmacology
  • Stilbenes / therapeutic use*


  • RNA, Messenger
  • Stilbenes
  • Nitric Oxide
  • L-Lactate Dehydrogenase
  • Nitric Oxide Synthase
  • Creatine Kinase
  • Resveratrol
  • NG-Nitroarginine Methyl Ester