LONG-TERM ADMINISTRATION OF L-ARGININE, L-NAME, AND THE EXOGENOUS NO DONOR MOLSIDOMINE MODULATES URINARY NITRATE AND CGMP EXCRETION IN RATS

Objective: The effects of long term oral administration of L-arginine, N-G-nitro-L-arginine methyl-ester (L-NAME), or molsidomine v placebo on blood pressure and the urinary excretion rates of NO3- and cyclic GMP were studied in Munich Wistar Fromter (MWF) rats. Methods: L-arginine (2 g.kg(-1) body weight, n = 8), N-G-nitro-L-arginine methylester (L-NAME; 5 mg.kg(-1), n = 8), or molsidomine (3 mg.kg(-1), n = 8) were given in drinking water and compared with placebo (n = 8) over a period of five months. Urinary excretion rates of NO3- (by gas chromatography) and cyclic GMP (by radioimmunoassay) were assessed in monthly intervals, as well as systolic blood pressure (tail plethysmography). Results: Mean basal blood pressure was 143.5(SEM 2.2) mm Hg. It was unaffected by L-arginine or molsidomine, but continuously and significantly increased during L-NAME treatment to 199.3(6.4) mm Hg (p < 0.05). Urinary excretion of NO3- increased by 20-41% nu controls in L-arginine and molsidomine treated rats (p < 0.05), and decreased by 5-15% in L-NAME treated rats (p < 0.05). Urinary excretion of cyclic GMP increased by 9-38% nu controls in the L-arginine and molsidomine treated groups and decreased by 5-20% in the L-NAME treated animals. Consistent with their higher blood pressure, L-NAME treated animals displayed cardiac hypertrophy. Conclusions: Determination of urinary NO3- excretion by gas chromatography is a sensitive and specific method to assess NO formation in vivo. Long term oral administration of L-arginine in MWF rats increases NO production (as assessed by the urinary excretion rates of NO3- and cyclic GMP), but does not significantly influence systolic bood pressure, whereas L-NAME induces sustained hypertension and cardiac hypertrophy due to inhibition of NO formation.