Ischemic acute renal failure in the rat: effects of L-arginine and superoxide dismutase on renal fun
May 1st, 2008 | by admin |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 L, Seibold A, Schneider R, Zimmermann J, Netzer KO, Wanner C.
Division of Nephrology, Department of Medicine, Julius-Maximilians-University, Würzburg - Germany.