INVOLVEMENT OF ENDOGENOUS DOPAMINE AND DA-1 RECEPTORS IN THE RENAL EFFECTS OF ATRIAL-NATRIURETIC-FACTOR IN RATS

The precise mechanism of the diuretic and natriuretic effects of Atrial Natriuretic Factor (ANF) is still unclear. The present study was undertaken with the aim of elucidating the mechanism of interaction between ANF, dopamine (DA) and DA receptors in the renal effects of ANF in rats. In pentobarbital anesthetized rats, ANF infusion (10-mu-g/kg/hour) produced marked diuresis and natriuresis which was accompanied by significant hypotension, bradycardia and also a modest increase in glomerular filtration rate. However, there was no accompanying increase in urinary DA excretion during ANF infusion. Pretreatment with SCH 23390, a selective DA-1 receptor antagonist caused significant attenuation of the diuretic and natriuretic effects of ANF whereas the hemodynamic changes produced by ANF were still evident in SCH 23390 treated animals. Plasma ANF levels were elevated to the same magnitude in both the control and SCH 23390 treated groups. Pretreatment with carbidopa, a dopa decarboxylase inhibitor also significantly blunted the diuretic and natriuretic effects of ANF. The antagonism of the ANF-induced diuresis and natriuresis by SCH 23390 and carbidopa was comparable in magnitude. These results suggest that endogenous DA, via activation of DA-1 receptors plays a permissive role in the renal effects of ANF, perhaps by enhancing tubular responsiveness to ANF. However, there does not appear to be a stimulatory effect of ANF on renal DA production or release.