Chiou W F, Yen M H, Chen C F
National Research Institute of Chinese Medicine, Taipei, Taiwan.
Eur J Pharmacol. 1991 Oct 29;204(1):35-40. doi: 10.1016/0014-2999(91)90832-b.
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.
本实验旨在研究小檗碱抑制去氧肾上腺素诱导的离体肠系膜动脉收缩的机制。结果表明，小檗碱（10^(-7)-3×10^(-5) M）呈剂量依赖性地引起血管舒张，并且去除内皮后小檗碱的血管舒张作用减弱。两种已知的内皮源性舒张因子（EDRF）抑制剂，L-NG-硝基精氨酸（L-NOARG）（L-精氨酸生成一氧化氮的特异性抑制剂）和亚甲蓝（可溶性鸟苷酸环化酶抑制剂），显著减弱了对小檗碱的血管舒张反应。此外，小檗碱与其他血管舒张剂一样，对去氧肾上腺素或高钾引起的相位性和紧张性收缩反应有不同影响。小檗碱（3×10^(-7) M）显著抑制去氧肾上腺素诱导的相位性收缩，但与维拉帕米不同，对高钾诱导的收缩无影响。此外，小檗碱消除了无钙/乙二醇双四乙酸（EGTA）培养基中咖啡因诱导的收缩。总之，小檗碱使大鼠肠系膜动脉血管舒张部分是通过间接释放EDRF，但主要是通过直接阻断细胞内钙库释放Ca2+来实现的。
