Mechanism of vasodilatory effect of berberine in rat mesenteric artery

The aim of this experiment was to study the mechanism by which berberine inhibits phenylephrine-induced contractions in isolated mesenteric arteries. The results show that berberine (10(-7)-3 x 10(-5) M) induced a dose-dependent vasodilation, and that the vasorelaxant effect of berberine was attenuated by the removal of the endothelium. Two known inhibitors of endothelium-derived relaxing factor (EDRF), L-NG-nitro arginine (L-NOARG) (a specific inhibitor of nitric oxide formation from L-arginine) and methylene blue (an inhibitor of soluble guanylyl cyclase), significantly attenuated the vasodilator response to berberine. In addition, berberine, like other vasodilators, differently affected the phasic and tonic contractile response elicited by either phenylephrine or high potassium. Berberine (3 x 10(-7) M) significantly inhibited the phasic contraction induced by phenylephrine but, in contrast to verapamil, had no effect on the high potassium-induced contraction. Moreover, berberine abolished the caffeine-induced contraction in Ca(2+)-free/EGTA medium. In conclusion, berberine vasodilates the rat mesenteric artery in part by indirectly releasing EDRF but mainly by directly blocking the release of Ca2+ from internal stores.