Contribution of nitric oxide to the protective effects of ischemic preconditioning in ischemia-reperfused rat kidneys

J Lab Clin Med. 2001 Jul;138(1):50-8. doi: 10.1067/mlc.2001.115648.


We examined the contribution of nitric oxide (NO) to the effect of ischemic preconditioning (IP) on renal function and the hemodynamics in ischemia-reperfusion (I/R) mediated kidney injury. IP was performed by using 4 minutes of ischemia followed by a 30-minute reperfusion interval. I/R treatment consisted of a 30-minute ischemia and 60-minute reperfusion interval. We measured the glomerular filtration rate (GFR), the fractional excretion of sodium (FE(Na)), and the renal blood flow (RBF) in IP+I/R and I/R kidneys. Rats were pretreated with NaCl, N(G)-nitro-L-arginine methyl ester (L-NAME), or L-arginine. We found that IP significantly improved GFR and FE(Na) as compared with I/R treatment; however, this effect was completely abolished by L-NAME injection and enhanced by L-arginine treatment. L-NAME treatment significantly diminished RBF but did not alter nitrite/nitrate excretion. Furthermore, we found that IP alone does not lead to inducible NO synthase protein expression whereas I/R or IP+I/R treatment clearly did. Moreover, we observed an increased heme oxygenase-1 expression in IP+I/R kidneys as compared with I/R treated ones. Our results clearly showed that IP pretreatment protects kidneys from I/R mediated tissue injury and that these effects were partially mediated by NO.

MeSH terms

  • Animals
  • Arginine / pharmacology
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Caspase 3
  • Caspases / metabolism
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Glomerular Filtration Rate / drug effects
  • Glomerular Filtration Rate / physiology
  • HSP70 Heat-Shock Proteins / metabolism
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase-1
  • Ischemic Preconditioning*
  • Kidney / blood supply
  • Kidney / enzymology*
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / metabolism*
  • Sodium / urine


  • Enzyme Inhibitors
  • HSP70 Heat-Shock Proteins
  • Nitric Oxide
  • Arginine
  • Sodium
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • NG-Nitroarginine Methyl Ester