Ischemic acute renal failure in the rat: effects of L-arginine and superoxide dismutase on renal function.
BACKGROUND
Regulation of renal hemodynamics -- especially intraglomerular hemodynamics -- is closely related to the L-arginine (L-Arg)/nitric oxide (NO) pathway, both under basal conditions and in acute renal failure (ARF). Also, superoxide anions -- which may react with NO -- play a role in ischemic ARF. L-Arg not only has beneficial effects on glomerular filtration rate (GFR) but also reduces O2(-) production and prevents NO synthase isoform I up-regulation. Thus, it is of interest to elucidate whether the potential beneficial effects of L-Arg in reperfusion can be augmented by additional treatment with superoxide dismutase (SOD).


METHODS
ARF was induced by renal artery clamping for 40 minutes. Animals were treated with either L-Arg, SOD, a combination of both, or saline. GFR, renal plasma flow (RPF), filtration fraction (FF) and blood pressure were recorded at baseline, after induction of ARF, during drug infusion and thereafter.


RESULTS
Renal artery clamping induces a severe drop of GFR, RPF and FF, which all are improved by L-Arg and SOD. Increasing GFR is mainly due to better renal perfusion. FF fell after reperfusion and increased with L-Arg and SOD, indicating improvement of disturbed intrarenal hemodynamics. Combined administration of L-Arg and SOD showed similar effects in comparison with each substance alone, but did not induce additional effects on GFR and RPF.


CONCLUSIONS
L-Arg and SOD exert beneficial effects in ischemic ARF. Probably, improvements in reducing NO availability and in enhancing O2(-) formation are both playing a mediating role. The underlying mechanisms regulating the interplay between NO availability and O2(-) formation need to be elucidated in further studies using -- aside from other means -- selective NOS inhibitors, intervention in different experimental phases and treatment for a longer period.
Schramm
Lothar
L
Division of Nephrology, Department of Medicine, Julius-Maximilians-University, Würzburg, Germany. l.schramm@dialyse-wuerzburg.de
Seibold
Alexandra
A
Schneider
Reinhard
R
Zimmermann
Josef
J
Netzer
Kai-Olaf
KO
Wanner
Christoph
C
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D001794:Blood Pressure; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000098:blood supply*; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017595:Renal Plasma Flow; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D016166:Free Radical Scavengers; D009569:Nitric Oxide; D001120:Arginine; D013482:Superoxide Dismutase