Antivasospastic effects of hydroxyfasudil,a Rho-kinase inhibitor,after subarachnoid hemorrhage

We investigated the anti-vasospastic potential of fasudil's active metabolite,hydroxyfasudil,a rho-kinase inhibitor,after subarachnoid hemorrhage (sah) and also its effect on hemorheological abnormalities following cerebral ischemia. chronic cerebral vasospasm was produced using a two-hemorrhage canine model. on day 7,angiographic vasospasm was observed in all animals,and intravenous administration of hydroxyfasudil (3 mg·kg -1·30 min -1) significantly reversed the vasospasm (predose diameter of the basilar artery,57.9% ± 2.0% of the baseline before the injection of blood; postdose diameter,64.5% ± 1.9%). the viscosity of whole blood was significantly increased 24 h after 1 h middle cerebral artery occlusion in rats. hydroxyfasudil (3 and 10 mg/kg,i.p.) significantly decreased blood viscosity. the specificity of hydroxyfasudil was examined against a panel of 17 protein kinases using elisa analysis. hydroxyfasudil inhibited rho-kinase α and β at a concentration of 10 μm by 97.6% and 97.7%,respectively. no other protein kinase was inhibited with 10 μm hydroxyfasudil by over 40%. the present results indicate hydroxyfasudil is a selective inhibitor of rho-kinase. the results also suggest that hydroxyfasudil contributes to the potency of fasudil to prevent cerebral vasospasm and hyperviscosity and suggest the potential utility of hydroxyfasudil as a therapeutic agent for patients with sah. © the japanese pharmacological society.