The natriuretic response to a dopamine DA(1) agonist requires endogenous activation of dopamine DA(2) receptors

Dopamine produced in the kidney acts as a natriuretic hormone by inhibiting tubular Na+, K+-ATPase activity. Previous in vitro studies have shown that Na+, KC-ATPase activity in the proximal tubule is inhibited by a synergistic action of dopamine 1 (DA(1)) and dopamine 2 (DA(2)) receptors. This in vivo study, performed on rats, investigates whether the natriuretic response to DA requires a synergistic action of DA(1) and DA(2) receptors. The DA(1) agonist, fenoldopam, significantly increased urinary sodium excretion, but there was no increase in sodium excretion when a DA(1) agonist was given together with a DA(2) antagonist. Neither DA(1) nor DA(2) antagonists had any influence on sodium excretion. The natriuretic response to fenoldopam was also significantly attenuated after the administration of benserazide, which inhibits aromatic acid decarboxylase and thereby suppresses the endogenous production of dopamine. In conclusion, the natriuretic effect of dopamine depends on the activation of both DA(1) and DA(2) receptors. The DAP receptor appears to be constitutively activated by endogenous dopamine.