Locally produced dopamine (DA) causes a reversible and dose-dependent inhibition in Na⁺-K⁺-ATPase activity in rat proximal tubule (PT) segments [A. Aperia, A. Bertorello, and I. Seri. Am. J. Physiol. 252 (Renal Fluid Electrolyte Physiol. 21): F32–F45, 1987.]. To examine whether this effect might be of physiological importance, rats were given normal-salt (NS) or high-salt (HS) diet for 10 days. HS diet significantly increased Na excretion but did not alter glomerular filtration rate (GFR). Benserazide (Bz), an inhibitor of the enzyme L-aromatic amino acid decarboxylase (AADC) that converts L-dopa to DA, significantly attenuated the natriuresis in HS rats but had no effect on GFR. By use of immunofluorescence (IF) studies AADC was localized to the PT. Specific AADC IF was not observed in the medulla. In AADC-positive PT segments, Na⁺-K⁺-ATPase activity was significantly lower in HS rats than in NS rats (P less than 0.001). In AADC-negative medullary thick ascending limb, Na⁺-K⁺-ATPase activity was the same in NS and HS rats. If HS rats were given Bz just before study, PT Na⁺-K⁺-ATPase activity increased significantly and was not different from Na⁺-K⁺-ATPase activity in PT segments from NS rats. Bz had no significant effect on PT Na⁺-K⁺-ATPase activity in NS rats. In PT segments from Bz-treated rats, DA inhibited Na⁺-K⁺-ATPase activity already at a dose of 10(-8) M, whereas in segments from NS rats, significant inhibition of Na⁺-K⁺-ATPase activity was not observed until DA was increased to 10(-7) M.(ABSTRACT TRUNCATED AT 250 WORDS)