Renal ischemia-reperfusion injury: Contribution of nitric oxide and renal blood flow

The contributions of nitric oxide (NO) and renal blood flow (RBF) were exam ined in ischemia-reperfusion injury in the rat kidney. The function of both kidneys was assessed by glomerular filtration rate (GFR), and fractional e xcretion of sodium (FENa), calculated before, during unilateral renal arter y clamping (45 min), and following reperfusion (90 min). RBF was measured i n the same model by ultrasonic flowmetry. Intrarenal NO levels were modulat ed by administration of S-nitroso-N-acetylpenicillamine (SNAP), L-arginine, acetylcholine, and the NO synthase inhibitor N-G-nitro-L-arginine methyl e ster (Lr NAME). SNAP increased GFR from 0.20 +/- 0.04 ml/min in control isc hemic kidney to 0.38 +/- 0.06 ml/min and reduced FENa from 19.3 +/- 3.4 to 9.5 +/- 1.8% Similar results were observed when L arginine was administered . Acetylcholine had no effect on GFR or FENa. RBF was fully restored within 60 min following reperfusion, with no change in the rate of recovery by L- arginine. L-NAME aggravated the ischemia-reperfusion injury, preventing ful l restoration of RBF, further reducing GFR and worsening FENa. In conclusio n ischemia-reperfusion injury ends in low intrarenal levels of NO. We propo se that this low NO level results from damage to the endothelial receptor s ignal transduction process and is not due to impaired NO synthase activity or to changes in RBF.