The mechanism of resveratrol-induced vasorelaxation differs in the mesenteric resistance arteries of lean and obese rats Available to Purchase

Resveratrol has been shown to induce vasorelaxation. In this study, we investigated the mechanism(s) of resveratrol-induced vasorelaxation in resistance mesenteric arteries from male lean and dietary-induced obese rats. Compared with lean rats, arteries from dietary-obese rats showed significant (P < 0.001) endothelial dysfunction, as indicated by a decrease (> 20%) in maximal acetylcholine-induced vasorelaxation. Resveratrol (5–35 µmol/l) induced concentration-dependent relaxation of mesenteric arteries preconstricted with noradrenaline (8 µmol/l) or KCl (125 mmol/l) from both lean and dietary-obese rats. There were no significant differences between the two groups, achieving a maximum relaxation of > 95% at a concentration of 35 µmol/l. In noradrenaline-preconstricted arteries from lean rats, N^G-nitro-L-arginine methyl ester (L-NAME; 100 and 300 µmol/l) caused a significant (P < 0.01) concentration-dependent rightward shift in reseveratrol activity, with no effect on maximal responses. However, L-NAME (100 and 300 µmol/l) did not alter the effects of reseveratrol on arteries from dietary-obese rats, giving superimposed concentration–responses curves. Indomethacin was also ineffective in altering resveratrol activity in arteries from both lean and dietary-obese rats. In noradrenaline-precontracted arteries from dietary-obese rats, responses to resveratrol were not attenuated by endothelial denudation, indicating an action independent of the endothelium. This study indicates that: (a) the maximal effects of resveratrol on resistance arteries from lean and dietary-obese rats are not effected by endothelial dysfunction, and (b) the effects of resveratrol in lean animals (where endothelial function is not impaired), but not in dietary-obese rats, are mediated via NO.