NITRIC-OXIDE SYNTHESIS AND L-ARGININE IN UREMIA

Nitric oxide (NO), an L-arginine derivative, is implicated in neuronal transmission, immune response and vasodilation, and acts as a modulat or of platelet function. Recent studies in the experimental model of r enal mass reduction (RMR) in rats have generated the hypothesis that a bnormalities in the NO synthetic pathway could play a key role in medi ating 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 wo rsens with time in close correlation with signs of renal injury This a bnormality is due to a major defect in inducible NO synthase (iNOS) co ntent in the kidney. In the same model, administration of either the N O precursor, L-arginine, or a NO-releasing compound reduces proteinuri a, slows renal disease progression, and prolongs survival. In contrast , in the systemic circulation of uremic rats, NO is formed in excessiv e amounts, possibly caused by higher release from systemic vessels due to the augmented expression of both iNOS and endothelial NOS. Up-regu lation of systemic NO synthesis might be a defense mechanism against u remic hypertension. On the other hand, a greater availability of NO to circulating cells may sustain the bleeding tendency, a well-known com plication of uremia.