The possible implication of trans-Resveratrol in the cardioprotective effects of long-term moderate wine consumption.
trans-Resveratrol (t-RESV; 1-10 microM), a phenolic component of wines, had no effect on phenylephrine-(PE; 1 microM) 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 by N(G)-nitro-L-arginine (L-NOARG; 0.1 mM) and methylene blue (10 microM), but they were unaffected by atropine (10 microM) and yohimbine (1 microM). The reversal effect produced by L-NOARG was antagonized by L-arginine but not by D-arginine (0.1 mM). t-RESV (1-10 microM) 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 microM) was ineffective in scavenging superoxide anions (O(2)*) 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 of t-RESV in rat aorta seems to be caused by the inhibition of vascular NADH/NADPH oxidase and the subsequent decrease of basal cellular O(2)* 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.
Orallo
Francisco
F
Departamentos de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Santiago de Compostela (La Coruña), España. fforallo@usc.es
Alvarez
Ezequiel
E
Camiña
Mercedes
M
Leiro
José Manuel
JM
Gómez
Eva
E
Fernández
Pilar
P
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013237:Stereoisomerism; D013267:Stilbenes / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*; D014969:Xanthine Oxidase / Q000378:metabolism
D002316:Cardiotonic Agents; D009097:Multienzyme Complexes; D013267:Stilbenes; D013481:Superoxides; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D014969:Xanthine Oxidase; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D000077185:Resveratrol