Role of CSE-Produced H2S on Cerebrovascular Relaxation via RhoA-ROCK Inhibition and Cerebral Ischemia-Reperfusion Injury in Mice

The role of CSE-produced H2S on cerebrovascular relaxation and cerebral ischemia-reperfusion (I/R) injury was investigated using CSE knockout (CSE–/–) and wild-type (CSE+/+) mice. The relaxation of the cerebral basilar artery (BA) to CSE-produced H2S and its mechanism were detected. The results revealed that both NaHS, a donor of exogenous H2S, and ROCK inhibitor Y27632 could induce significant relaxation of the BA, but the relaxation of the BA to NaHS was significantly attenuated by Y27632. In addition, removal of endothelium could reduce the relaxation of the BA to Y27632; CSE knockout also significantly attenuated Y27632-induced BA relaxation with endothelium rather than without endothelium. By contrast, the contraction of the BA from CSE–/– mice to RhoA agonist LPA or U46619 was stronger than that from CSE+/+ mice. Furthermore, RhoA activity and ROCK protein expression remarkably increased in the BA vascular smooth muscle cells (VSMCs) from CSE–/– mouse, which were inhibited by NaHS pretreatment. Thes...