Protective effect of nitric oxide on ischemia/reperfusion-induced renal injury and endothelin-1 overproduction

Eur J Pharmacol. 2005 Jul 11;517(3):232-9. doi: 10.1016/j.ejphar.2005.05.026.


To elucidate the role of nitric oxide (NO) in the pathogenesis of ischemic acute renal failure, we examined the effects of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409) and N(G)-nitro-L-arginine methyl ester (L-NAME) as a NO donor and a non-selective NO synthase inhibitor on ischemia/reperfusion-induced renal injury and renal endothelin-1 content. Ischemic acute renal failure was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. At 24 h after reperfusion, renal function in untreated acute renal failure rats markedly decreased and histological examination revealed severe renal damage. In addition, increases in renal endothelin-1 contents were evident in the acute renal failure rats at 2, 6, and 24 h after reperfusion, respectively. Pretreatment with FK409 (1 or 3 mg/kg, i.v.) attenuated ischemia/reperfusion-induced renal dysfunction, histological damage, and endothelin-1 overproduction after reperfusion. In contrast, pretreatment with L-NAME (1 or 10 mg/kg, i.v.) aggravated renal injuries of acute renal failure rats at 24 h after reperfusion, and the effect is accompanied by further increases in the renal endothelin-1 content at 2 and 6 h, but not at 24 h, after reperfusion. These results suggest that suppressive effects of NO on the renal endothelin-1 overproduction induced by ischemia/reperfusion in an early phase are probably responsible for the protective effect of NO against ischemic acute renal failure.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Endothelin-1 / biosynthesis*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Function Tests
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / physiology*
  • Nitric Oxide Donors / pharmacology*
  • Nitro Compounds / pharmacology
  • Protective Agents / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Renal Insufficiency / metabolism
  • Renal Insufficiency / physiopathology
  • Renal Insufficiency / prevention & control*
  • Reperfusion Injury / physiopathology*
  • Time Factors


  • Endothelin-1
  • Nitric Oxide Donors
  • Nitro Compounds
  • Protective Agents
  • Nitric Oxide
  • FK 409
  • NG-Nitroarginine Methyl Ester