Infusion of ANP to rats results in an inhibition of Na(+)-H+ antiport and Na(+)-Pi symport in brush border membrane vesicles (BBMV) prepared from kidneys of these animals (J Clin Invest 75:1983). iIn the present study we investigated the intrarenal mechanism by which infused ANP elicits these changes in proximal tubular transport systems. As in rats, infusion of ANP to rabbits resulted in a diuresis, natriuresis, and increase in GFR; however, unlike in rats, the fractional excretion of phosphate (Pi) was not changed. In BBMV prepared from cortices of ANP-infused rabbits, the rate of Na(+)-H+ antiport was decreased (delta -27%), but Na+ gradient-dependent uptakes of Pi and L-proline were not different from controls. Incubation of rabbit cortical tubule suspension in vitro with ANP 10(-7) M alone had no inhibitory effect on Na(+)-H+ antiport in BBMV prepared from these tubules, whereas incubation with other hormonal agents, 1 U/ml PTH (delta 61%) or with dopamine (DA) 10(-4) M (delta -34%), did inhibit the rate of Na(+)-H+ antiport in BBMV from the same pool of tubules. However, when tubules were incubated in the presence of (10(-5) M) DA, the addition of 10(-7) M ANP did cause a significant (delta -21%) decrease in Na(+)-H+ antiport activity in BBMV. In contrast, ANP did not show similar inhibitory effect in the presence of submaximal inhibitory doses of PTH. To explore whether ANP may act on proximal tubules in vivo indirectly, via mediation of DA, we evaluated the effect of ANP on some parameters of catecholamine system in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)