Cardiology Department, First Hospital of China Medical University, North 2nd Road No.92, Heping Ward, Shenyang 110001, China.
Int J Cardiol. 2011 Apr 14;148(2):168-73. doi: 10.1016/j.ijcard.2009.10.051. Epub 2009 Nov 26.
Vasoconstriction and vascular hypersensitivity to serotonin has been described previously in animal models of adventitia injury. The present study was undertaken to investigate the contribution of the RhoA/Rho-kinase pathway to the collar-induced the change of vascular contractility and reactivity in rat carotid artery.
Wistar Kyoto rats were assigned to 4 treatments (n=12): vehicle, fasudil, valsartan, and fasudil plus valsartan. After 1 week of treatment, adventitia injury was induced by positioning a silicone collar around the right carotid artery for 1 week. Blood flow and vascular reactivity to serotonin was determined 1 week after injury, and carotids were harvested for morphometry and biochemical analysis.
Adventitia injury leaded to histological changes of vasoconstriction with the percent lumen patency of 54.5 ± 4.3% (p<0.001) decreasing, accompanying by the reduction of the blood flow (2.79 ± 0.22 ml/min vs. 3.67 ± 0.26 mi/min/p<0.001) when compared to contralateral arteries. The increase of vascular reactivity sensitivity to serotonin was observed in the collared artery when compared with the contralateral artery. Treatment with valsartan and fasudil prevented the development of vasoconstriction, improved the carotid blood flow and normalized the hypersensitivity to serotonin. Injury increased Angiotensin II type 1(AT(1)receptor, Rho-kinase, and p-MYPT1(Thr696) expression. Valsartan lowered the Rho-kinase and p-MYPT1(Thr696) expression. Fasudil inhibited the p-MYPT1(Thr696) expression.
Collar-induced adventitia injury resulted in the enhancement of vascular contractility and reactivity. The activation of RhoA/Rho-kinase signal pathway, stimulated by AT(1) receptor, plays an important role in the collar-induced the change of vascular contractility and reactivity.
先前在血管外膜损伤的动物模型中已经描述了血管收缩和对 5-羟色胺的血管超敏性。本研究旨在探讨 RhoA/Rho 激酶通路对套管诱导的大鼠颈动脉硬化性收缩和反应性改变的贡献。
将 Wistar Kyoto 大鼠分为 4 组（n=12）：载体、法舒地尔、缬沙坦和法舒地尔加缬沙坦。治疗 1 周后，将硅胶套管置于右侧颈总动脉周围 1 周，诱导血管外膜损伤。损伤后 1 周测定血流和血管对 5-羟色胺的反应性，并取颈动脉进行形态计量学和生化分析。
血管外膜损伤导致血管收缩的组织学变化，管腔通畅率为 54.5±4.3%（p<0.001），与对侧动脉相比，血流量减少（2.79±0.22ml/min 对 3.67±0.26ml/min，p<0.001）。与对侧动脉相比，套管动脉观察到血管对 5-羟色胺反应性敏感性增加。缬沙坦和法舒地尔治疗可预防血管收缩，改善颈总动脉血流并使对 5-羟色胺的敏感性正常化。损伤增加了血管紧张素 II 型 1（AT1 受体）、Rho 激酶和 p-MYPT1（Thr696）的表达。缬沙坦降低 Rho 激酶和 p-MYPT1（Thr696）的表达。法舒地尔抑制 p-MYPT1（Thr696）的表达。
套管诱导的血管外膜损伤导致血管收缩性和反应性增强。AT1 受体刺激的 RhoA/Rho 激酶信号通路的激活在套管诱导的血管收缩性和反应性改变中起重要作用。
