文献类型：期刊文献

英文题名：Ferulic acid relaxed rat aortic, small mesenteric and coronary arteries by blocking voltage-gated calcium channel and calcium desensitization via dephosphorylation of ERK1/2 and MYPT1

作者：Zhou, Zhong-Yan[1,2,3];Xu, Jia-Qi[1];Zhao, Wai-Rong[1];Chen, Xin-Lin[1];Jin, Yu[4];Tang, Nuo[1];Tang, Jing-Yi[1,5]

机构：[1]Shanghai Univ Tradit Chinese Med, Longhua Hosp, Shanghai 200032, Peoples R China;[2]Univ Macau, State Key Lab Qual Res Chinese Med, Macau, Peoples R China;[3]Univ Macau, Inst Chinese Med Sci, Macau, Peoples R China;[4]East China Univ Sci & Technol, Sch Pharm, Engn Res Ctr Pharmaceut Proc Chem, Shanghai 200032, Peoples R China;[5]Shanghai Univ Tradit Chinese Med, Shanghai 200032, Peoples R China

年份：2017

卷号：815

起止页码：26

外文期刊名：EUROPEAN JOURNAL OF PHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000413780700004)】；

基金：This study was supported by Research Funds for Construction of Public Health System of Shanghai (GWIV-28), National Natural Science Foundation of China (81603549), Fundamental Research Funds from Health and Family Planning Commission of Shanghai (20154Y0052), and Science and Technology Commission of Shanghai (14401972501)

语种：英文

外文关键词：Ferulic acid; Vasorelaxation; Calcium sensitization; Calcium channel; Endothelium

摘要：Ferulic acid, a natural ingredient presents in several Chinese Materia Medica such as Radix Angelicae Sinensis, has been identified as an important multifunctional and physiologically active small molecule. However, its pharmacological activity in different blood vessel types and underlying mechanisms are unclear. The present study was to investigate the vascular reactivity and the possible action mechanism of FA on aorta, small mesenteric arteries and coronary arteries isolated from Wistar rats. We found FA dose-dependently relieved the contraction of aorta, small mesenteric arteries and coronary arteries induced by different contractors, U46619, phenylephrine (Phe) and KCl. The relaxant effect of FA was not affected by L-NAME (eNOS inhibitor), ODQ (soluble guanylate cyclase inhibitor), and mechanical removal of endothelium in thoracic aortas. The contraction caused by 60 mM KCl (60 K) was concentration-dependently hindered by FA pretreatment in all three types of arteries. In Ca2+-free 60 K solution, FA weakened Ca2+-related contraction in a concentration dependent manner. And FA relaxed both fluoride and phorbol ester which were PKC, ERK and Rho-kinase activators induced contraction in aortic rings with or without Ca2+ in krebs solution. Western blotting experiments in A7r5 cells revealed that FA inhibited calcium sensitization via dephosphorylation of ERK1/2 and MYPT1. Furthermore, the relaxation effect of FA was attenuated by verapamil (calcium channel blocker), ERK inhibitor, and fasudil (ROCK inhibitor). These results provide evidence that FA exhibits endothelium-independent vascular relaxant effect in different types of arteries. The molecular mechanism of vasorelaxation activity of FA probably involved calcium channel inhibition and calcium desensitization.