Endothelium-dependent contraction and direct relaxation induced by baicalein in rat mesenteric artery.

The vascular effect of purified baicalein from Scutellaria baicalensis Georgi (Huangqin) was examined in rat isolated mesenteric arteries. Baicalein exerts both contractile and relaxant effects on the U46619-, phenylephrine- or high K+-contracted endothelium-intact arteries. In endothelium-denuded arteries, the contractile response to baicalein (0.3-10 microM) was absent while the relaxant response to baicalein (30-300 microM) remained. Pretreatment with 100 microM N(G)-nitro-L-arginine (L-NNA) or 3 microM methylene blue abolished the baicalein-induced contraction while 10 microM indomethacin or 100 nM BQ610 had no effect. Pretreatment with baicalein (3-10 microM) significantly attenuated the relaxation induced by acetylcholine or by A23187. In contrast, baicalein did not affect the sodium nitroprusside-induced relaxation in endothelium-denuded arteries. Baicalein also concentration dependently inhibited the contractile response to 1 microM phorbol 12,13-diacetate (PDA) in Ca2+-free solution. Baicalein had little effect on the contractile response to 60 mM K+ or to 10 mM caffeine in endothelium-denuded arteries. The baicalein-induced relaxation was unaffected by 1 microM glibenclamide or by 3 mM tetraethylammonium ions in endothelium-denuded arteries. These results indicate that baicalein at low concentrations caused a contractile response and inhibited the endothelium-dependent relaxation, probably through inhibition of endothelial nitric oxide (NO) formation/release. At higher concentrations, baicalein relaxed the arterial smooth muscle partially through inhibition of the protein kinase C-mediated contractile mechanism.