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

• Published in: The Journal of laboratory and clinical medicine 2001-07, Vol.138 (1), p.50-58
• Main Authors: Ogawa, Toshihisa, Nussler, Andreas K., Tuzuner, Eda, Neuhaus, Peter, Kaminishi, Michio, Mimura, Yoshikazu, Beger, Hans G.
• Format: Article
• Language: English
• Subjects: Animals; Arginine - pharmacology; Biological and medical sciences; 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; Heme Oxygenase (Decyclizing) - metabolism; Heme Oxygenase-1; HSP70 Heat-Shock Proteins - metabolism; Ischemic Preconditioning; Kidney - blood supply; Kidney - enzymology; Kidneys; Male; Medical sciences; Nephrology. Urinary tract diseases; 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; Urinary system involvement in other diseases. Miscellaneous
• ISSN: 0022-2143; 1532-6543
• 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 (FENa), and the renal blood flow (RBF) in IP+I/R and I/R kidneys. Rats were pretreated with NaCl, NG-nitro-L-arginine methyl ester (L-NAME), or L-arginine. We found that IP significantly improved GFR and FENa 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. (J Lab Clin Med 2001;138:50-8)