L-Arginine counteracts nitric oxide deficiency and improves the recovery phase of ischemic acute renal failure in rats.
BACKGROUND
In ischemic acute renal failure (ARF), nitric oxide-dependent regulation of renal hemodynamics and glomerular function is disturbed. Previous studies indicate that the nitric oxide precursor l-arginine (l-Arg) has beneficial effects on renal function. Here we further analyzed the impact of l-Arg on functional and biochemical parameters of nitric oxide signaling during the course of ischemic ARF.


METHODS
Ischemic ARF was induced in rats by bilateral clamping of renal arteries for 45 minutes. l-Arg was applied intraperitoneally during clamping, and orally during 14 days of follow-up. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured, and biochemical parameters analyzed by protein immunoblots.


RESULTS
Clamping resulted in 70% to 90% reduction of GFR and RPF, with a gradual recovery by day 14. Using an in situ assay with the oxidative fluorescent dye hydroethidine, increased tubular generation of O2- was detected in the early course of ischemic ARF, indicating enhanced oxidative stress. These findings were accompanied by up-regulation of the nitric oxide receptor, soluble guanylate cyclase, and by significant regulatory changes of inducible nitric oxide synthase (iNOS) and endothelial NOS expression. l-Arg had a beneficial effect on GFR and RPF, decreased O2- production, diminished up-regulation of soluble guanylate cyclase, and prevented up-regulation of iNOS.


CONCLUSIONS
Ischemic ARF is accompanied by marked alterations in the expression of key enzymes of the nitric oxide pathway, indicative for deficiency of constitutive NOS activity. l-Arg supplementation reduces O2- generation and significantly improves the expression of nitric oxide signaling proteins as well as the recovery phase of ischemic ARF.
Schneider
Reinhard
R
Division of Nephrology, Department of Medicine, Julius-Maximilians-University, Würzburg, Germany.
Raff
Ulrike
U
Vornberger
Nicole
N
Schmidt
Monika
M
Freund
Ralf
R
Reber
Mark
M
Schramm
Lothar
L
Gambaryan
Stepan
S
Wanner
Christoph
C
Schmidt
Harald H H W
HH
Galle
Jan
J
D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism; D006207:Half-Life; D007511:Ischemia / Q000150:complications*; D009569:Nitric Oxide / Q000172:deficiency*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012079:Renal Circulation / Q000187:drug effects; D012995:Solubility; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase