INHIBITION OF RENAL NITRIC-OXIDE SYNTHESIS WITH N(G)-MONOMETHYL-L-ARGININE AND N(G)-NITRO-L-ARGININE

In barbiturate-anesthetized dogs, the effects of intrarenal infusion of the two selective inhibitors of nitric oxide synthesis, N(G)-monomethyl-L-arginine (L-NMMA) and N(G)-nitro-L-arginine (NO-Arg), were compared. Basal renal blood flow (RBF) was reduced by 15 +/- 2% after L-NMMA at 0.28-mu-mol/ml, by 20 +/- 3% after NO-Arg at 0.07-mu-mol/ml, and by 31 +/- 5% after NO-Arg at 0.56-mu-mol/ml. Endothelium-dependent vasodilation induced by intrarenal infusion of acetylcholine was unaltered after L-NMMA, reduced by 24 +/- 3% after NO-Arg at 0.07-mu-mol/ml, and reduced by 59 +/- 13% after NO-Arg at 0.56-mu-mol/ml. Endothelium-independent vasodilation induced by intrarenal infusion of atrial natriuretic factor was not reduced after L-NMMA and NO-Arg. This study shows that NO-Arg is more potent than L-NMMA in inhibiting basal renal nitric oxide synthesis. In contrast to L-NMMA, NO-Arg exerted an inhibitory effect on acetylcholine-induced renal vasodilation. Our findings indicate that one-third of the basal RBF and more than one-half of the increase in RBF during acetylcholine infusion are dependent on nitric oxide synthesis.