title: Nitric oxide synthesis and L-arginine in uremia.
abstract: Nitric oxide (NO), an L-arginine derivative, is implicated in neuronal transmission, immune response and vasodilation, and acts as a modulator of platelet function. Recent studies in the experimental model of renal mass reduction (RMR) in rats have generated the hypothesis that abnormalities in the NO synthetic pathway could play a key role in mediating the complex hemodynamic and hemostatic disorders associated with the progression of renal disease. Thus, renal NO generation is lower than normal in rats with RMR 7 days after surgery and progressively worsens with time in close correlation with signs of renal injury. This abnormality is due to a major defect in inducible NO synthase (iNOS) content in the kidney. In the same model, administration of either the NO precursor, L-arginine, or a NO-releasing compound reduces proteinuria, slows renal disease progression, and prolongs survival. In contrast, in the systemic circulation of uremic rats, NO is formed in excessive amounts, possibly caused by higher release from systemic vessels due to the augmented expression of both iNOS and endothelial NOS. Up-regulation of systemic NO synthesis might be a defense mechanism against uremic hypertension. On the other hand, a greater availability of NO to circulating cells may sustain the bleeding tendency, a well-known complication of uremia.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Bergamo, Italy. aiello@irfmn.mnegri.it
authors.forename: S
authors.initials: S
authors.lastname: Aiello
authors.forename: M
authors.initials: M
authors.lastname: Noris
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000201:enzymology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D014511:Uremia / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase