title: Role of nitric oxide in the renal protective effects of ischemic preconditioning.
abstract: Possible involvement of nitric oxide (NO) in the protective effect of ischemic preconditioning against the ischemia/reperfusion-induced acute renal failure was investigated. Ischemic preconditioning, which consists of three cycles of 2-minute ischemia followed by 5-minute reperfusion, was performed prior to 45-minute ischemia. Ischemic preconditioning significantly improved the renal dysfunction induced by 45-minute ischemia followed by 24-hour reperfusion. Histopathological examination of the kidney of ischemia/reperfusion rats revealed severe renal damage, and suppression of the damage was seen with the ischemic preconditioning treatment. NO metabolites (NOx) production in the kidney after 45-minute ischemia and reperfusion was markedly increased in ischemia/reperfusion rats with ischemic preconditioning, compared with animals not subjected to ischemic preconditioning, and these increases correlated with changes in endothelial NO synthase (eNOS) protein expression in renal tissues. The improvement of renal dysfunction in ischemic preconditioning rats was abolished by the pretreatment with NG-nitro-L-arginine, a nonselective NOS inhibitor, but not with aminoguanidine, an inducible NOS inhibitor. In addition, increment of endothelin-1 (ET-1) content in the kidney after the reperfusion was markedly suppressed by ischemic preconditioning treatment. These findings suggest that the protective effect of ischemic preconditioning on ischemia/reperfusion -induced acute renal failure is closely related to the renal nitric oxide production following the increase in eNOS expression after the reperfusion and that the suppressive effect of ischemic preconditioning on the ischemia/reperfusion -induced renal ET-1 overproduction may be partly involved in the ameliorating effect of ischemic preconditioning.
authors.affiliation: Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Yamashita
authors.forename: Masaya
authors.initials: M
authors.lastname: Ogata
authors.forename: Makoto
authors.initials: M
authors.lastname: Itoh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamasowa
authors.forename: Yuka
authors.initials: Y
authors.lastname: Shimeda
authors.forename: Masanori
authors.initials: M
authors.lastname: Takaoka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Matsumura
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D001806:Blood Urea Nitrogen; D019332:Endothelin-1 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D019194:Ischemic Preconditioning / Q000379:methods*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D019332:Endothelin-1; D004791:Enzyme Inhibitors; D006146:Guanidines; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C004479:pimagedine