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

We examined the contribution of nitric oxide (NO) to the effect of ischemic preconditioning (IP) on renal function and the hemodynamics in ischemia-re perfusion (I/R) mediated kidney injury. IP was performed by using 4 minutes of ischemia followed by a 30-minute reperfusion interval, I/R treatment co nsisted of a 30-minute ischemia and 60-minute reperfusion interval, We meas ured the glomerular filtration rate (GFR), the fractional excretion of sodi um (FENa), and the renal blood flow (RBF) in IP+I/R and I/R kidneys. Rats w ere pretreated with NaCl, N-G-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 significa ntly diminished RBF but did not alter nitrite/nitrate excretion. Furthermor e, we found that IP alone does not lead to inducible NO synthase protein ex pression whereas I/R or IP+I/R treatment clearly did. Moreover, we observed an increased heme oxygenase-l expression in IP+I/R kidneys as compared wit h I/R treated ones. Our results clearly showed that IP pretreatment protect s kidneys from I/R mediated tissue injury and that these effects were parti ally mediated by NO.