Selective dopamine-1 receptor stimulation produces natriuresis by a direct tubular action

Fenoldopam mesylate, a selective dopamine-1 (DA-1) receptor agonist, was infused intravenously in 10 normal male subjects in metabolic balance. The study was designed to determine the mechanism of dopamine-induced natriuresis. During fenoldopam infusion renal plasma flow (RPF) and urine flow rate manifested a biphasic response. The RPF rose from 344 +/- 39 to 481 +/- 44 ml/min (P less than 0.05), decreased to control levels, and then rose to 497 +/- 38 ml/min (P less than 0.05). Urinary sodium excretion (UNaV) and fractional excretion of sodium (FENa) demonstrated a sustained increase during DA-1 receptor activation. The FENa rose from 1.6 +/- 0.1 to 2.7 +/- 0.6% (P less than 0.05). Glomerular filtration rate (GFR), blood pressure and heart rate were unchanged. Our results, specifically the dissociation of RPF from UNaV and FENa, demonstrate in man that stimulation of renal tubular DA-1 receptors causes natriuresis.