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. These findings revealed that the CSE-produced H2S induced cerebrovascular relaxation is generated from endothelial cells and the mechanism of vascular relaxation may relate to inhibition of RhoA-ROCK pathway. We next sought to confirm the protective effect of CSE-produced H2S on cerebral I/R injury produced by middle cerebral artery occlusion and bilateral common carotid artery occlusion in mice. We investigated the changes of neurological deficit, cerebral infarct, brain water content, LDH decrease, MDA increase as well as impairment of learning and memory function. The results showed that the cerebral injury became more grievous in CSE-/-mice than that in CSE+/+mice, which could be remarkably alleviated by NaHS pretreatment.
Keywords: Hydrogen sulfide; RhoA-ROCK pathway; cerebral basilar artery; ischemia/reperfusion; learning and memory function.