Cao Yong-Xiao, Zhang Wei, He Jian-Yu, He Lang-Chong, Xu Cang-Bao
Department of Pharmacology, Xi'an Jiaotong University School of Medicine, and Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, PR China.
Vascul Pharmacol. 2006 Sep;45(3):171-6. doi: 10.1016/j.vph.2006.05.004. Epub 2006 May 19.
The purpose of the present study was to investigate the effect of ligustilide on vasodilatation in rat mesenteric artery and the mechanisms responsible for it. Isometric tension of rat mesenteric artery rings was recorded by a sensitive myograph system in vitro. The results showed that ligustilide at concentrations more than 10 microM relaxed potassium chloride (KCl)-preconstricted rat mesenteric artery in a concentration-dependent manner. The vasodilatation effect of ligustilide was not dependent on endothelium. Ligustilide rightwards shifted concentration-response curves induced by KCl, calcium chloride (CaCl(2)), noradrenaline (NA) or 5-hydroxytryptamine (5-HT) in a non-parallel manner. This suggests that the vasodilatation effects were most likely via voltage-dependent calcium channel (VDCC) and receptor-operated calcium channel (ROCC). Propranolol, glibenclamide, tetraethylammonium and barium chloride did not affect the vasodilation induced by ligustilide, showing that beta-adrenoceptor, ATP sensitive potassium channel, calcium-activated potassium channel and inwardly rectifying potassium channel were not involved in the vasodilatation. Ligustilide concentration-dependently inhibited the vasoconstriction induced by NA or CaCl(2) in Ca(2+)-free medium, indicating that the vasodilatation relates to inhibition of extracellular Ca(2+) influx through VDCC and ROCC, and intracellular Ca(2+) release from Ca(2+) store. Since caffeine-induced contraction was inhibited by ligustilide, inhibition of intracellular Ca(2+) released by ligustilide occurred via the ryanodine receptors. Our results suggest that ligustilide induces vasodilatation in rat mesenteric artery by inhibiting the VDCC and ROCC, and receptor-mediated Ca(2+) influx and release.
本研究的目的是探讨藁本内酯对大鼠肠系膜动脉血管舒张的影响及其作用机制。采用灵敏的肌动描记系统体外记录大鼠肠系膜动脉环的等长张力。结果表明，浓度超过10微摩尔的藁本内酯能以浓度依赖的方式舒张氯化钾（KCl）预收缩的大鼠肠系膜动脉。藁本内酯的血管舒张作用不依赖于内皮。藁本内酯使由KCl、氯化钙（CaCl₂）、去甲肾上腺素（NA）或5-羟色胺（5-HT）诱导的浓度-反应曲线非平行右移。这表明血管舒张作用很可能是通过电压依赖性钙通道（VDCC）和受体操纵性钙通道（ROCC）介导的。普萘洛尔、格列本脲、四乙铵和氯化钡不影响藁本内酯诱导的血管舒张，表明β-肾上腺素能受体、ATP敏感性钾通道、钙激活钾通道和内向整流钾通道不参与血管舒张。藁本内酯在无钙培养基中浓度依赖性地抑制NA或CaCl₂诱导的血管收缩，表明血管舒张与抑制细胞外Ca²⁺通过VDCC和ROCC内流以及细胞内Ca²⁺从Ca²⁺储存库释放有关。由于藁本内酯抑制了咖啡因诱导的收缩，藁本内酯抑制细胞内Ca²⁺释放是通过兰尼碱受体实现的。我们的结果表明，藁本内酯通过抑制VDCC和ROCC以及受体介导的Ca²⁺内流和释放来诱导大鼠肠系膜动脉血管舒张。
