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

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.
AuthorsKohji Teraishi, Hayato Kurata, Atsushi Nakajima, Masanori Takaoka, Yasuo Matsumura
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 505 Issue 1-3 Pg. 205-11 (Nov 28 2004) ISSN: 0014-2999 [Print] Netherlands
PMID15556154 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Amides
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Pyridines
  • Y 27632
  • Peroxidase
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases
Topics
  • Acute Kidney Injury (etiology, physiopathology, prevention & control)
  • Amides (pharmacology)
  • Animals
  • Enzyme Inhibitors (pharmacology)
  • Intracellular Signaling Peptides and Proteins
  • Kidney (drug effects, metabolism, pathology)
  • Kidney Function Tests
  • Male
  • Peroxidase (metabolism)
  • Protein-Serine-Threonine Kinases (antagonists & inhibitors)
  • Pyridines (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (complications)
  • Time Factors
  • rho-Associated Kinases

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