No abstract

Resveratrol, a natural antioxidant and polyphenol found in grapes and wine, has been found to pharmacologically precondition the heart through the upregulation of nitric oxide (NO). To gain further insight of the role of NO in resveratrol preconditioning, mouse hearts devoid of any copies of inhibitory NO synthase (iNOS) (iNOS knockout) and corresponding wild-type hearts were perfused with 10 microM resveratrol for 15 min followed by 25 min of ischemia and 2 h of reperfusion. Control experiments were performed with wild-type and iNOS knockout hearts that were not treated with resveratrol. Resveratrol-treated wild-type mouse hearts displayed significant improvement in postischemic ventricular functional recovery compared with those of nontreated hearts. Both resveratrol-treated and nontreated iNOS knockout mouse hearts resulted in relatively poor recovery in ventricular function compared with wild-type resveratrol-treated hearts. Myocardial infarct size was lower in the resveratrol-treated wild-type mouse hearts compared with other group of hearts. In concert, a number of apoptotic cardiomyocytes was lower in the wild-type mouse hearts treated with resveratrol. Cardioprotective effects of resveratrol was abolished when the wild-type mouse hearts were simultaneously perfused with aminoguanidine, an iNOS inhibitor. Resveratrol induced the expression of iNOS in the wild-type mouse hearts, but not in the iNOS knockout hearts, after only 30 min of reperfusion. Expression of iNOS remained high even after 2 h of reperfusion. Resveratrol-treated wild-type mouse hearts were subjected to a lower amount of oxidative stress as evidenced by reduced amount of malonaldehyde content in these hearts compared with iNOS knockout and untreated hearts. The results of this study demonstrated that resveratrol was unable to precondition iNOS knockout mouse hearts, whereas it could successfully precondition the wild-type mouse hearts, indicating an essential role of iNOS in resveratrol preconditioning of the heart.

Reactive oxygen species have been implicated in the pathophysiology of renal ischemia reperfusion injury. Antioxidants including polyphenolics have been found to protect renal cells from the cellular injury induced by ischemia and reperfusion. Resveratrol, a stilbene polyphenol found in grapes and red wine, has recently been found to protect isolated rat heart from ischemia reperfusion injury. This study was sought to determine if resveratrol could also protect renal cells from ischemic injury. Male Wistar rats were treated with control, resveratrol (0.23 microg/kg), vehicle used to solubilize resveratrol, and resveratrol plus L-NAME (15 mg/kg body wt), a nitric oxide blocker. Our results demonstrated that resveratrol administration reduced the mortality of ischemic rats from 50% to 10% and renal damage was reduced as indicated by histologic examination and serum creatinine level. The short-term administration of resveratrol also inhibited renal lipid peroxidation induced by ischemia and reperfusion both in cortex and in medulla. Electron paramagnetic resonance detected an increased formation of nitric oxide in the resveratrol-treated kidney that was reduced to the baseline value after treating the rats with L-NAME in addition to resveratrol. The results suggest that resveratrol reduced the renal ischemia reperfusion injury through a nitric oxide-dependent mechanism.