DOSE-RESPONSE ANALYSIS OF THE EFFECTS OF FENOLDOPAM, A DOPAMINE-1 RECEPTOR AGONIST, ON RENAL-FUNCTION

The present study was carried out to perform a dose-response analysis of the effect of fenoldopam, a DA-1 receptor agonist, on renal sodium excretion. Infusions of fenoldopam for 30 min at doses of 0.125, 0.25, 0.5, and 1.0-mu-g/kg/min in four separate groups of pentobarbital-anesthetized dogs caused dose-dependent hypotension and renal vasodilation. The reflex tachycardic response was not dose-dependent and seen only with the three higher doses. There was no change in glomerular filtration with any of the four doses of fenoldopam. At the doses of 0.25 and 0.5-mu-g/kg/min fenoldopam caused significant increases in urine volume, urinary sodium excretion, and fractional excretion of sodium during the infusion as well as during the first recovery period of 30 min. At the highest dose of 1-mu-g/kg/min no diuresis or natriuresis was seen during the infusion; however, significant increases in urine volume and sodium excretion were seen during the two recovery periods. At the lowest dose (0.125-mu-g/kg/min) fenoldopam caused minimal hemodynamic changes but produced maximum increases in urine volume and urinary sodium excretion. These effects of fenoldopam were antagonized by the DA-1 receptor antagonist, SCH 23390. The results of our study show that the tubular effects of fenoldopam leading to increased renal sodium excretion are evident at doses lower than those required to cause changes in systemic and renal hemodynamics. In addition, at higher doses when the magnitude of hypotension is very pronounced, this effect may limit the increase in sodium excretion produced by fenoldopam.