The Possible Implication of trans-Resveratrol in the Cardioprotective Effects of Long-Term Moderate Wine Consumption

doi:10.1124/mol.61.2.294

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Vol. 61, Issue 2, 294-302, February 2002

**The Possible Implication of trans-Resveratrol in the Cardioprotective Effects of Long-Term Moderate Wine Consumption**

Francisco Orallo, Ezequiel Álvarez, Mercedes Camiña, José Manuel Leiro, Eva Gómez, and Pilar Fernández

Departamentos de Farmacología (F.O., E.Á., M.C.) y Microbiología y Parasitología (J.M.L.), Facultad de Farmacia; Departamento de Farmacología, Facultad de Medicina y Odontología (E.G., P.F.), Universidad de Santiago de Compostela, Santiago de Compostela (La Coruña), España

trans-Resveratrol (t-RESV; 1-10 µM), a phenolic component of wines, had no effect on phenylephrine-(PE; 1 µM) and high KCl-(60mM) induced contractions in endothelium-denuded rat aortic rings.However, it relaxed the contractile response produced by thesevasoconstrictor agents in intact rat aorta. The vasorelaxing effectsof t-RESV were completely inhibited by N^G-nitro-L-arginine (L-NOARG; 0.1 mM) and methylene blue (10 µM),but they were unaffected by atropine (10 µM) and yohimbine (1µM). The reversal effect produced by L-NOARG was antagonized byL-arginine but not by D-arginine (0.1 mM). t-RESV (1-10 µM) didnot significantly modify rat aorta constitutive nitric-oxide synthaseactivity. However, this natural compound decreased NADH/NADPHoxidase activity in rat aortic homogenates. In addition, t-RESV(1-10 µM) was ineffective in scavenging superoxide anions (O₂ &cjs1138; )generated enzymatically by a hypoxanthine/xanthine oxidase (HX/XO)system and/or to inhibit XO. The above data demonstrate that thecharacteristic endothelium-dependent vasorelaxant effect of t-RESVin rat aorta seems to be caused by the inhibition of vascularNADH/NADPH oxidase and the subsequent decrease of basal cellularO₂ &cjs1138; generation and, therefore, of NO biotransformation. Underthe assumption that t-RESV exhibits a similar behavior in humanblood vessels and bearing in mind that an overactivity of NADH/NADPHoxidase has been found in a number of cardiovascular pathologies,the results obtained in this work suggest that t-RESV could playan important role in the cardioprotective effects induced by thelong-term moderate wineconsumption.

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