Vasodilatation produced by orientin and its mechanism study.
In this paper we investigated the vascular activity and possible mechanism of Orientin, from bamboo leaves (Phyllostachys nigra), in isolated thoracic aortic rings from New Zealand rabbit. Among the four compounds, studied, only Orientin relaxed phenylephrine-induced contractions with an IC50 value of 2.28 microM in the endothelium intact and with an IC50 value around 7.27 microM in the endothelium removed aortic rings. The vasorelaxant effect of Orientin on endothelium-intact thoracic aortic rings was attenuated by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester, but not by indomethacin (a cyclooxygenase inhibitor), tetraethylammonium chloride (K+ channels inhibitor) or propranolol (beta-receptor inhibitor). Furthermore, Orientin inhibited norepinephrine (NE), CaCl2 and KCl-induced vasoconstriction concentration dependently in a non-competitive manner, and also reduced both the initial fast release and the sustained phases of phenylephrine-induced contractions. Orientin can stimulate NO production from endothelial cells. Orientin also increased cyclic guanosine 3,5-cyclic monophosphate (cGMP) levels without changes in adenosine-3',5'-cyclic phosphoric acid (cAMP) in rabbit aorta. The results showed that Orientin relaxed thoracic aortic rings by the nitric oxide-cGMP pathway, and in the vascular smooth muscle inhibited the contraction induced by the activation of receptor-operating and voltage-dependent Ca2+ channels. Cyclooxygenase pathway, potassium channels, beta-receptors and cAMP pathway, on the other hand, had no apparent roles. The inhibition of both intracellular Ca2+ release and extracellular Ca2+ influx may be one of the main vasorelaxant mechanisms of Orientin.
Fu
Xiao-Chun
XC
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China.
Wang
Min-Wei
MW
Li
Shao-Peng
SP
Zhang
Ying
Y
Wang
Huai-Liang
HL
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D015220:Calcium Channels / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D015220:Calcium Channels; D005419:Flavonoids; D005960:Glucosides; D009569:Nitric Oxide; D006152:Cyclic GMP; C065886:orientin