Abstract
trans-Resveratrol (t-RESV; 1–10 μM), a phenolic component of wines, had no effect on phenylephrine-(PE; 1 μM) and high KCl-(60 mM) induced contractions in endothelium-denuded rat aortic rings. However, it relaxed the contractile response produced by these vasoconstrictor agents in intact rat aorta. The vasorelaxing effects of t-RESV were completely inhibited byN G-nitro-l-arginine (l-NOARG; 0.1 mM) and methylene blue (10 μM), but they were unaffected by atropine (10 μM) and yohimbine (1 μM). The reversal effect produced by l-NOARG was antagonized byl-arginine but not by d-arginine (0.1 mM).t-RESV (1–10 μM) did not significantly modify rat aorta constitutive nitric-oxide synthase activity. However, this natural compound decreased NADH/NADPH oxidase activity in rat aortic homogenates. In addition, t-RESV (1–10 μM) was ineffective in scavenging superoxide anions (O2⨪) generated enzymatically by a hypoxanthine/xanthine oxidase (HX/XO) system and/or to inhibit XO. The above data demonstrate that the characteristic endothelium-dependent vasorelaxant effect oft-RESV in rat aorta seems to be caused by the inhibition of vascular NADH/NADPH oxidase and the subsequent decrease of basal cellular O2⨪ generation and, therefore, of NO biotransformation. Under the assumption that t-RESV exhibits a similar behavior in human blood vessels and bearing in mind that an overactivity of NADH/NADPH oxidase has been found in a number of cardiovascular pathologies, the results obtained in this work suggest that t-RESV could play an important role in the cardioprotective effects induced by the long-term moderate wine consumption.
- The American Society for Pharmacology and Experimental Therapeutics
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