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
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
复制标题
阿魏酸通过阻断电压门控钙通道和通过 ERK1/2 和 MYPT1 去磷酸化实现钙脱敏来放松大鼠主动脉、小肠系膜和冠状动脉。
DOI：
10.1016/j.ejphar.2017.10.008
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发表时间：
2017-11-15
影响因子：
5
通讯作者：
Tang, Jing-Yi
中科院分区：
文献类型：
--
作者：
Zhou, Zhong-Yan;Xu, Jia-Qi;Tang, Jing-Yi
阿魏酸是一种具有多种生理活性的多功能小分子化合物，广泛存在于中药中。然而，其在不同血管类型中的药理活性和潜在机制尚不清楚。本研究旨在探讨FA对Wistar大鼠主动脉、肠系膜小动脉和冠状动脉的血管反应性及其可能的作用机制。结果表明，FA能剂量依赖性地减轻U46619、苯丙氨酸（Phe）和KCl引起的主动脉、肠系膜小动脉和冠状动脉的收缩。FA的舒张作用不受L-NAME（eNOS抑制剂）、ODQ（可溶性鸟苷酸环化酶抑制剂）和机械去除内皮的影响。在所有三种类型的动脉中，由60 mM KCl（60 K）引起的收缩被FA预处理浓度依赖性地阻碍。在无Ca ~（2+）的60 K溶液中，FA以浓度依赖性方式减弱Ca ~（2+）相关的收缩。FA对PKC、ERK和Rho激酶激活剂氟和佛波酯引起的离体主动脉环的收缩均有舒张作用。在A7 r5细胞中的蛋白质印迹实验显示，FA通过ERK 1/2和MYPT 1的去磷酸化来抑制钙致敏。此外，维拉帕米（钙通道阻滞剂），ERK抑制剂和法舒地尔（ROCK抑制剂）减弱FA的舒张作用。这些结果为FA在不同类型动脉中具有非内皮依赖性血管舒张作用提供了证据。FA舒张血管活性的分子机制可能与抑制钙通道和钙脱敏有关。
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.