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Eur J Pharmacol. 2004 Nov 28;505(1-3):205-11.

Preventive effect of Y-27632, a selective Rho-kinase inhibitor, on ischemia/reperfusion-induced acute renal failure in rats.

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1
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

Abstract

We evaluated the effects of Y-27632 [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate], a selective Rho-kinase inhibitor, on ischemic acute renal failure. Ischemic acute renal failure in rats was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after the contralateral nephrectomy. Y-27632 administration (1, 10, and 100 microg/kg, i.p.) before ischemia dose-dependently attenuated the ischemia/reperfusion-induced renal dysfunction and histological damage, such as tubular necrosis. The ischemia/reperfusion-induced renal dysfunction was also overcome by postischemic treatment with Y-27632 at 100 microg/kg, i.p. Myeloperoxidase activity in the kidney after ischemia/reperfusion was significantly increased, being the maximal level at 6 h after the reperfusion, and this increase was also suppressed by Y-27632 (100 microg/kg, i.p.). These results indicate that Y-27632 prevents the development of ischemia/reperfusion-induced acute renal failure, and the effect is related to the suppression of the enhanced myeloperoxidase activity in an early phase after reperfusion, thereby suggesting that the Rho/Rho-kinase pathway plays a key role in the pathogenesis of ischemic acute renal failure.

PMID:
15556154
DOI:
10.1016/j.ejphar.2004.10.040
[Indexed for MEDLINE]

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