Resveratrol Increases Vascular Oxidative Stress Resistance

Epidemiological studies suggest that Mediterranean diets rich in resveratrol are associated with reduced risk of coronary artery disease. However, the mechanisms by which resveratrol exerts its vasculoprotective effects are not completely understood. Because oxidative stress and endothelial cell injury play a critical role in vascular aging and atherogenesis, we evaluated whether resveratrol inhibits oxidative stress‐induced endothelial apoptosis. We found that exposure of cultured aortic segments and endothelial cells to oxidative stressors (H2O2, paraquat, ultraviolet light) elicited significant increases in caspase 3/7 activity, which were prevented by resveratrol pre‐treatment (10‐6 to 10‐4 mol/L). Both acute (1 h) and chronic (24 h) resveratrol treatment significantly attenuated UV254 and paraquat‐induced H2O2 generation (DCF fluorescence) in cultured arteries. Resveratrol also effectively scavenged H2O2 in a cell‐free DCF assay. Resveratrol treatment up‐regulated the expression of glutathione peroxidase and catalase in cultured arteries, whereas it had no significant effect on expression of SOD isoforms. Thus, resveratrol seems to increase vascular oxidative stress resistance by scavenging H2O2 and preventing oxidative stress‐induced endothelial cell death. We propose that the anti‐oxidant and anti‐apoptotic effects of resveratrol, together with its previously described anti‐inflammatory actions, are responsible, at least in part, for its cardioprotective effects. (Grant support: AHA 0430108N, 0435140N, NIH HL077256, Philip Morris USA).