Involvement of Rho-kinase in collar-induced vasoconstriction and vascular hypersensitivity to serotonin in rat carotid

Abstract Background 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. Methods 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. Results 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（AT1 ）receptor, Rho-kinase, and p-MYPT1Thr696 expression. Valsartan lowered the Rho-kinase and p-MYPT1Thr696 expression. Fasudil inhibited the p-MYPT1Thr696 expression. Conclusions Collar-induced adventitia injury resulted in the enhancement of vascular contractility and reactivity. The activation of RhoA/Rho-kinase signal pathway, stimulated by AT1 receptor, plays an important role in the collar-induced the change of vascular contractility and reactivity.