PHYSIOLOGICAL-ROLE OF NITRIC-OXIDE IN REGULATION OF RENAL-FUNCTION INHUMANS

The physiological role of endogenous nitric oxide in regulation of ren al function in humans is unclear. Eight healthy men received an inhibi tor of nitric oxide synthase, N-G-monomethyl-L-arginine (L-NMMA, 3 mg/ kg), and saline placebo intravenously on two occasions. L-NMMA signifi cantly increased mean arterial pressure (+7%) and total peripheral res istance(+36%). However, because renal plasma flow did not decrease sig nificantly, the increase in renal vascular resistance (+21%) was signi ficantly less than the increase in total peripheral resistance; Glomer ular filtration rate (-19%), filtration fraction (-10%), urine flow ra te (-18%), sodium (-28%), and free water excretion (-25%) all decrease d significantly. Fractional distal, but not proximal, sodium reabsorpt ion increased. L-NMMA also significantly decreased plasma nitrate and urinary excretion of nitrate and dopamine. There were no significant c hanges in plasma renin activity, plasma endothelin, and aldosterone or in platelet number and ex vivo aggregation. L-NMMA had a plasma half- life of 75 min. Basal generation of nitric oxide appears to contribute less to vascular tone in the kidney than systemically but may alter a fferent arteriolar tone. Decreased fractional sodium excretion support s an important physiological role for nitric oxide in inhibition of tu bular sodium reabsorption, possibly mediated by the renal dopaminergic system.