The Effect of Selective Dopamine-1 Receptor Stimulation on Renal and Adrenal Function in Man*

Abstract

We studied the actions of iv fenoldopam, a selective opamine-1 (DA-1) receptor agonist, in 10 normal men eating a diet containing 150 meq sodium and 60 meq potassium per day. During DA-1 receptor stimulation systemic hemodynamic function did not change. Fenoldopam resulted in an increase in urine flow rate from 13 ± 1 (±SE) to a peak of 17 ± 2 mL/min (P < 0.05) and an increase in renal plasma flow from 344 ± 39 to 481 ± 44 mL/min (P < 0.05). Urinary sodium excretion and fractional excretion of sodium both increased. Urinary sodium excretion rose to a maximum of 0.32 ± 0.05 compared with a control value of 0.21 ± 0.03 meq/min (P < 0.01), while fractional excretion of sodium rose to 2.7 ± 0.6 compared with a control value of 1.6 ± 0.1% (P < 0.05). The glomerular filtration rate did not change. Administration of a predominantly DA-2 antagonist during continuous DA-1 receptor stimulation did not block the fenoldopam-induced natriuresis. The rise in plasma aldosterone concentration after metoclopramide administration was blunted by DA-1 receptor activation [19.2 ± 2.9 during control compared with 12.7 ± 1.3 ng/dL (P < 0.01) during fenoldopam]. No change occurred in serum potassium, plasma cortisol, or PRA. We conclude that selective DA-1 receptor stimulation in man produces sustained natriuresis and inhibition of aldosterone release by direct renal and adrenal effects.