| Autor: |
Shin-ichi Satoh, Masakazu Takayasu, Koh Kawasaki, Ichiro Ikegaki, Asako Hitomi, Kazuo Yano, Masato Shibuya, Toshio Asano |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Předmět: |
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| Zdroj: |
Journal of Pharmacological Sciences, Vol 118, Iss 1, Pp 92-98 (2012) |
| Druh dokumentu: |
article |
| ISSN: |
1347-8613 |
| DOI: |
10.1254/jphs.11075FP |
| Popis: |
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. Keywords:: Rho-kinase, hydroxyfasudil, subarachnoid hemorrhage, vasospasm, hemodynamic dysfunction |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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