Preventive effect of Y-27632, a selective Rho-kinase inhibitor, on ischemia/reperfusion-induced acute renal failure in rats.
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.
Teraishi
Kohji
K
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Kurata
Hayato
H
Nakajima
Atsushi
A
Takaoka
Masanori
M
Matsumura
Yasuo
Y
D058186:Acute Kidney Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications*; D013997:Time Factors; D054460:rho-Associated Kinases
D000577:Amides; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; C108830:Y 27632; D009195:Peroxidase; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases