Wang Sheng-Peng, Zang Wei-Jin, Kong Shan-Shan, Yu Xiao-Jiang, Sun Lei, Zhao Xin-Feng, Wang Shi-Xiang, Zheng Xiao-Hui
Department of Pharmacology, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, China.
Eur J Pharmacol. 2008 Jan 28;579(1-3):283-8. doi: 10.1016/j.ejphar.2007.10.009. Epub 2007 Oct 13.
The present study was designed to investigate the relaxant effect of isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP), a new metabolite from Salvia miltiorrhiza, on rat mesenteric artery. Isolated mesenteric arterial rings were mounted in organ baths and the isometric tension changes were measured continuously by a sensitive myograph system. The results showed that IDHP at concentrations greater than 0.1 nM produced a concentration-dependent relaxation of artery contracted by norepinephrine with pEC(50) of 7.41+/-0.08. Removal of the endothelium did not affect this relaxation, suggesting that IDHP exerted a direct effect on vascular smooth muscle cells. Meanwhile, the vasorelaxant effect of IDHP was unaffected by pre-treatment with ATP-sensitive K(+) channel inhibitor glibenclamide, delayed rectifier K(+) channel inhibitor 4-aminopyridine, inwardly rectifying K(+) channel inhibitor barium chloride and beta-adrenoceptor antagonist propranolol. However, the non-specific K(+) channel inhibitor tetraethylammonium (TEA, 3 mM) produced a rightward shift of 1.8 fold on the concentration-response curve of IDHP. Moreover, IDHP shifted the concentration-response curve of CaCl(2) as well as two receptor-mediated constrictors, phenylephrine and 5-hydroxytryptamine, to the right in a non-parallel manner. In the absence of extracellular Ca(2+), IDHP depressed the contractions induced by norepinephrine and CaCl(2), and the maximal inhibitions were 48.3+/-18.9% and 58.4+/-10.9%, respectively. These results suggest that IDHP exerts a vasorelaxant effect by inhibiting both Ca(2+) release from intracellular stores and Ca(2+) influx through voltage-dependent calcium channels, and receptor-operated calcium channels in vascular smooth muscle cells. In addition, activation of vascular TEA-sensitive K(+) channels may be partially involved in the relaxant effect of IDHP.
本研究旨在探讨丹参新代谢产物3-(3,4-二羟基苯基)-2-羟基丙酸异丙酯（IDHP）对大鼠肠系膜动脉的舒张作用。将分离的肠系膜动脉环置于器官浴槽中，用灵敏的肌动描记系统连续测量等长张力变化。结果表明，浓度大于0.1 nM的IDHP能使去甲肾上腺素收缩的动脉产生浓度依赖性舒张，pEC(50)为7.41±0.08。去除内皮不影响这种舒张，提示IDHP对血管平滑肌细胞有直接作用。同时，IDHP的血管舒张作用不受ATP敏感性钾通道抑制剂格列本脲、延迟整流钾通道抑制剂4-氨基吡啶、内向整流钾通道抑制剂氯化钡和β-肾上腺素能受体拮抗剂普萘洛尔预处理的影响。然而，非特异性钾通道抑制剂四乙铵（TEA，3 mM）使IDHP的浓度-反应曲线右移1.8倍。此外，IDHP使氯化钙以及两种受体介导的收缩剂苯肾上腺素和5-羟色胺的浓度-反应曲线非平行右移。在无细胞外钙的情况下，IDHP抑制去甲肾上腺素和氯化钙诱导的收缩，最大抑制率分别为48.3±18.9%和58.4±10.9%。这些结果表明，IDHP通过抑制细胞内钙库释放钙以及通过电压依赖性钙通道和受体操纵性钙通道的钙内流来发挥血管舒张作用。此外，血管TEA敏感性钾通道的激活可能部分参与IDHP的舒张作用。
