NITRIC-OXIDE INCREASES RENAL BLOOD-FLOW BY INTERACTING WITH THE SYMPATHETIC NERVOUS-SYSTEM

To investigate whether changes in renal blood flow induced by nondepressor doses of L-arginine, the precursor of nitric oxide, are mediated by a sympathetic neural mechanism, we examined the following in conscious rabbits: (1) the effects of intravenous infusion of L- or D-arginine (15 to 200 mu mol/kg per minute) on renal blood flow and renal sympathetic nerve activity with or without intravenous infusion of a nonpressor dose of N-G-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase inhibitor, and (2) the effects of L-arginine on renal blood flow after renal denervation with or without L-NMMA pretreatment. In renal innervated rabbits, L-arginine (100 and 200 mu mol/kg per minute) increased renal blood flow by 9 +/- 2 and 16 +/- 3 mL/min (P<.05, respectively) and decreased renal sympathetic nerve activity by 12 +/- 4% and 19 +/- 3% of control (P<.05, respectively). In contrast, no changes occurred in any variable during D-arginine infusion. L-NMMA attenuated the renal blood flow and renal sympathetic nerve activity responses to L-arginine (P<.05). In renal denervated rabbits, L-NMMA also attenuated the renal blood flow responses to L-arginine (P<.05) and abolished them (P<.05) compared with those in renal innervated rabbits. All renal blood flow responses to L-arginine were accompanied by parallel changes in plasma L-citrulline concentration. These results indicate that exogenous L-arginine decreases renal sympathetic nerve activity and that the reduction in renal sympathetic nerve activity could contribute to the increase in renal blood flow as well as other actions of nitric oxide, such as a direct vasodilator action on vascular smooth muscle tone, suppression of adrenergic nerve transmission in the blood vessels, and inhibition of the release of vasoactive substances.