DL0805,a Rho-kinase inhibitor,attenuates angiotensinⅡ-induced vascular contraction in vitro by inhib

• 作 者: LILi;CHENBai-nian;GONGLi-li;FANGLian-hua;DUGuan-hua;
• 机 构: National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medica
• 出 处: 中国药理学会第十一次全国学术会议
• 发表日期: 2011年期

　　Angiotensin Ⅱ (Ang Ⅱ) activates Rho-kinase and initiates the contractile activity in vascular smooth muscle.In this study, we investigated the vasorelaxing effect of DL0805, a Rho-kinase inhibitor, on Ang Ⅱ-induced vascular contractions and its molecular mechanism of action.We found that DL0805 inhibited Ang Ⅱ-induced vascular contractions in both endothelium-intact and endothelium-denuded rat aortic tings.Furthermore, increased phosphorylation level of myosin light chain 2 (MLC2) at Ser19 by Ang Ⅱ stimulation was significantly attenuated by DL0805 in both endothelium-intact and-denuded rat aortic rings.Moreover, DL0805 significantly suppressed Ang Ⅱ-induced Ca2 + influx in VSMCs.In addition, DL0805 was found to block the increase in ERK1/2 phosphorylation at Thr202/Tyr204 in response to Ang Ⅱ in both rat aortic rings and VSMCs.These results demonstrate that DL0805 inhibits Ang Ⅱ-induced rat aortic rings contraction and the mechanism involves the inhibition of Ang Ⅱ-induced Ca2+ influx and ERK1/2 activation.