Endothelium-dependent vasodilatory effect of vitisin C, a novel plant oligostilbene from Vitis plants (Vitaceae), in rabbit aorta.

Abstract

We investigated the pharmacological properties of vitisin C, a novel plant oligostilbene from Vitis plants. Vitisin C (1-10 microM) dose-dependently inhibited the contractile responses of endothelium-intact rabbit thoracic aorta induced by phenylephrine (1 microM). These inhibitory effects were abolished in the presence of N (G)-nitro-L-arginine methyl ester (L-NAME; 300 microM), a potent inhibitor of nitric oxide synthase, but not atropine (1 microM), a non-selective muscarinic cholinoceptor antagonist. In endothelium-denuded rabbit aorta, vitisin C was ineffective in attenuating phenylephrine-induced contraction. Moreover, vitisin C (10 microM) increased cGMP production in endothelium-intact, but not endothelium-denuded, aorta, and this increase was abolished in the presence of L-NAME (300 microM). To assess Ca(2+) movement across the endothelial cell membrane induced by vitisin C, we further investigated (45)Ca(2+) influx into cultured rabbit aortic endothelial cells in the presence of vitisin C (3 microM), carbachol (1 microM) or A23187 (10 nM). Vitisin C and carbachol significantly enhanced (45)Ca(2+) influx, which was inhibited by nifedipine (10 microM), a blocker of L-type Ca(2+) channels. In the presence of SK&F96365, a blocker of receptor-operated Ca(2+) channels, (45)Ca(2+) influx induced by carbachol was significantly inhibited, whereas that induced by vitisin C was not affected. On the other hand, A23187 enhanced (45)Ca(2+) influx in the presence and absence of nifedipine and SK&F96365. These results suggest that vitisin C evokes endothelium-dependent vasorelaxation through enhancing nitric oxide release, which is facilitated by Ca(2+) influx into endothelial cells via nifedipine-sensitive Ca(2+) channels.