Intrarenal dopamine acts at the dopamine-1 receptor to control renal function

Exogenous dopamine increases renal blood flow and produces diuresis and natriuresis in mammalian species. Dopamine is produced intrarenally and dopamine-1 receptors have been demonstrated within the kidney. However, the role of intrarenal dopamine in the control of renal function is unknown. We studied the renal effects of a specific dopamine-1 antagonist, SCH 23390 (SCH, MW 398, Schering-Plough, Bloomfield, New Jersey, USA) infused into the renal artery of uninephrectomized conscious dogs (n = 5) in metabolic balance at a sodium intake of 40 mmol/day. The infusion of SCH at 0.01 pmol/kg per min did not change the urinary flow rate or urinary sodium excretion. Significant dose-dependent reductions in urine volume, urinary sodium excretion and fractional excretion of sodium were observed with intrarenal SCH administration at 0.1, 5.0 and 10 pmol/kg per min. Rebound diuresis and natriuresis occurred after cessation of SCH administration. There were no changes in renal haemodynamic function, systemic plasma renin activity (PRA), plasma aldosterone concentration or mean arterial pressure during intrarenal SCH administration. These results demonstrate for the first time that intrarenal dopamine controls renal function physiologically by acting at the renal dopamine-1 receptors.