Renal ischemia-reperfusion injury: contribution of nitric oxide and renal blood flow.
The contributions of nitric oxide (NO) and renal blood flow (RBF) were examined in ischemia-reperfusion injury in the rat kidney. The function of both kidneys was assessed by glomerular filtration rate (GFR), and fractional excretion of sodium (FENa), calculated before, during unilateral renal artery clamping (45 min), and following reperfusion (90 min). RBF was measured in the same model by ultrasonic flowmetry. Intrarenal NO levels were modulated by administration of S-nitroso-N-acetylpenicillamine (SNAP), L-arginine, acetylcholine, and the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). SNAP increased GFR from 0.20 +/- 0.04 ml/min in control ischemic 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 full restoration of RBF, further reducing GFR and worsening FENa. In conclusion, ischemia-reperfusion injury ends in low intrarenal levels of NO. We propose that this low NO level results from damage to the endothelial receptor signal transduction process and is not due to impaired NO synthase activity or to changes in RBF.
Mashiach
E
E
Eliachar Research Laboratory, Western Galilee Hospital, Nahariya, Israel. SHSELA@naharia.health.gov.il
Sela
S
S
Winaver
J
J
Shasha
S M
SM
Kristal
B
B
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D012964:Sodium / Q000652:urine; D014665:Vasodilator Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; C110881:S-nitro-N-acetylpenicillamine; D014665:Vasodilator Agents; D009569:Nitric Oxide; D001120:Arginine; D012964:Sodium; D010396:Penicillamine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester