Rolle des L-Arginin/NO-Stoffwechselweges im akuten Nierenversagen

Role of the L-arginine/NO-pathway in acute renal failure ■ Summary Regulation of renal hemodynamics – in particular intraglomerluar hemodynamics -is closely related to the L-arginine/ NO-pathway. Almost all forms of acute renal failure (ARF) are characterized by a reduction in renal plasma flow (RPF) and increased renal vascular resistance. NO, metabolized from L-arginine, is capable of improving renal function due to its vasorelaxing properties in almost all models of ARF, whereas unselective inhibition of nitric oxide synthase (NOS) generally exerts contrary effects. Increased tubular generation of oxygen radicals in the early course of ischemic ARF indicates increased oxidative stress. Simultaneously regulatory changes in expression of iNOS (inducible NOS) and eNOS (endothelial NOS) are observed. Apart from the positive functional effects with L-arginine supplementation a remarkable reduction in the formation of oxygen radicals and reduced overexpression of iNOS are observed. This is important, because in ischemic ARF increased expression of iNOS is accompanied by increased formation of oxygen radicals and peroxynitrite. Both substances are highly reactive and exert many cytotoxic effects. eNOS-derived NO probably plays such an important role in maintaining and improving renal and intraglomerular hemodynamics that negative effects from iNOS-derived NO are overcome. The roles of NOS are different for different types of NOS and also depend on the time course of ARF. Future management strategies should focus on the interplay between antioxidants and NO regulators and the correlation of reactive oxygen species and NO.