Endothelium-dependent vasodilatory effect of vitisin C, a novel plant oligostilbene from Vitis plants (Vitaceae), in rabbit aorta.
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.
Seya
Kazuhiko
K
Department of Pharmacology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Furukawa
Ken-Ichi
K
Taniguchi
Satoshi
S
Kodzuka
Genji
G
Oshima
Yoshiteru
Y
Niwa
Masatake
M
Motomura
Shigeru
S
D000818:Animals; D001011:Aorta; D001285:Atropine / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D006152:Cyclic GMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011817:Rabbits; D013267:Stilbenes / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*; D027843:Vitis
D001572:Benzofurans; D002121:Calcium Channel Blockers; D018679:Cholinergic Agonists; D007093:Imidazoles; D007476:Ionophores; D018727:Muscarinic Antagonists; D013267:Stilbenes; D014665:Vasodilator Agents; C477277:vitisin C; D000001:Calcimycin; D001285:Atropine; D002217:Carbachol; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester