ORAL SUPPLEMENTATION OF L-ARGININE PREVENTS CHRONIC CYCLOSPORINE NEPHROTOXICITY IN RATS

This study was performed to evaluate the effect of L-arginine (L-Arg) on the prevention of chronic cyclosporine (CsA) nephrotoxicity in rats . Rats pair-fed a low-salt diet (0.05%) were given CsA (15 mg/kg/day s .c.), CsA and L-Arg (L-Arg group, 1.25 g/l water), CsA and N-nitro-L-a rginine methyl ester (L-NAME group, 70 mg/l water) or vehicle. After 2 8 days, the L-Arg group had a higher glomerular filtration rate compar ed to the CsA (0.42+/-0.05 vs. 0.31+/-0.06 ml/min/100 g, p < 0.05) and the L-NAME groups (vs. 0.19+/-0.04 ml/min/100 g, p < 0.05) and a sign ificantly lower serum creatinine level compared to the CsA (0.70+/-0.0 6 vs. 0.92+/-0.12 mg/dl, p < 0.05) and the L-NAME groups (vs. 1.21+/-0 .17 mg/dl, p < 0.05). The L-Arg group had less fibrosis, tubular injur y (TI), and arteriolopathy than the CsA (fibrosis 0.39+/-0.14 vs. 0.74 +/-0.15: TI 1.3+/-0.3 vs. 2.0+/-0.1, arteriolopathy 33+/-7 vs. 48+/-17 , p < 0.05, respectively) and the L-NAME groups (fibrosis vs. 1.67+/-0 .32, TI vs. 2.6+/-0.3, arteriolopathy vs. 63+/-10, p < 0.05, respectiv ely). Plasma renin activity in the L-Arg group was less than in the Cs A (18+/-2 vs. 23+/-3 ng Ang I/ml/h, p < 0.05) and the L-NAME groups (v s. 30+/-3 ng Ang I/ml/h, p < 0.05). Nitric oxide production in L-Arg g roup was higher than in the CsA (24.2+/-1.7 vs. 11.1+/-1.5 rho mol/24 h, p < 0.05) and the L-NAME groups (vs. 8.4+/-1.0 mu mo1/24 h, p < 0.0 5). In conclusion, the nitric oxide pathway is associated with the pat hogenesis of chronic CsA nephrotoxicity, and exogenous L-Arg supplemen tation is effective in reducing chronic CsA nephrotoxicity in rats.