Hydrogen sulfide-mediated inhibition of ROCK exerts a vasoprotective effect on ischemic brain injury.

As a gas molecule, hydrogen sulfide (HS) exerts neuroprotective effects. Despite its recognized importance, there remains a need for a deeper understanding of HS's impact on vascular smooth muscle cells and its role in ischemic brain injury. This study employs encompassing cultured primary cerebral vascular smooth muscle cells, oxygen-glucose deprivation/reoxygenation model, in vitro vascular tone assessments, in vivo middle cerebral artery occlusion and reperfusion experimentation in male rats, and the utilization of Rho-associated coiled-coil containing protein kinase 2 () knockout, to unravel the intricate relationship between HS and cerebrovascular diastolic function. Our findings show that RhoA activation induces heightened vascular smooth muscle cell (VSMC) contraction, whereas the introduction of exogenous HS mitigates the relaxant effect of the middle cerebral artery in rats through the downregulation of both ROCK and ROCK, with ROCK exhibiting a more pronounced effect. Correspondingly, the attenuation of ROCK expression yields a more substantial reduction in the protective impact of HS on cerebral blood flow, as well as learning and memory ability in ischemic injury, compared with the decrease in ROCK expression. Moreover, we demonstrate that HS effectively mitigates the damage induced by oxygen-glucose deprivation/reoxygenation in male mouse primary vascular smooth muscle cells. This effect is characterized by enhanced cell proliferation, reduced lactate dehydrogenase leakage, elevated superoxide dismutase activity, and inhibited apoptosis. Notably, this protective effect is markedly diminished in cells derived from ROCK knockout mice. Our study reveals that HS can relax cerebral vascular smooth muscle and ameliorate ischemic stroke injury by inhibiting the ROCK, with a particular emphasis on the role of ROCK. This study employs a diverse array of methods; our collective findings indicate that HS safeguards against ischemic brain injury by inhibiting ROCK activity, thereby promoting relaxation of cerebral smooth muscle and mitigating the impairment of cerebral smooth muscle cell function caused by oxygen-glucose deprivation/reoxygenation. In addition, our data underscore the critical role of ROCK in mediating the cerebral protective effects of HS, surpassing that of ROCK.