Resveratrol Protects Myocardial Ischemia-Reperfusion Injury through Both No-Dependent and No-Independent Mechanisms

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 neuronal nitric oxide synthase ( nNOS) is unchanged. In animals preconditioned with resveratrol (0.5 to 1mg/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, 1mg/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. (C) 2004 Elsevier Inc. All rights reserved