We investigated the pharmacological properties of vitisin C, a novel plant oligostilbene from Vitis plants. Vitisin C (1-10 μM) dose-dependently inhibited the contractile responses of endothelium-intact rabbit thoracic aorta induced by phenylephrine (1 μM). These inhibitory effects were abolished in the presence of NG-nitro-L-arginine methyl ester (L-NAME; 300 μM), a potent inhibitor of nitric oxide synthase, but not atropine (1 μM), a non-selective muscarinic cholinoceptor antagonist. In endothelium-denuded rabbit aorta, vitisin C was ineffective in attenuating phenylephrine-induced contraction. Moreover, vitisin C (10 -M) increased cGMP production in endothelium-intact, but not endothelium-denuded, aorta, and this increase was abolished in the presence of L-NAME (300 μM). To assess Ca2+ movement across the endothelial cell membrane induced by vitisin C, we further investigated 45Ca2+ influx into cultured rabbit aortic endothelial cells in the presence of vitisin C (3 μM), carbachol (1 μM) or A23187 (10 nM). Vitisin C and carbachol significantly enhanced 45Ca2+ influx, which was inhibited by nifedipine (10 μM), a blocker of L-type Ca2+ channels. In the presence of SK&F96365, a blocker of receptor-operated Ca2+ channels, 45Ca2+ influx induced by carbachol was significantly inhibited, whereas that induced by vitisin C was not affected. On the other hand, A23187 enhanced 45Ca2+ 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 Ca2+ influx into endothelial cells via nifedipine-sensitive Ca2+ channels.
- Nifedipine-sensitive Ca channel
- Rabbit thoracic aorta
- Vitisin C
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