The effects of fenoldopam, a selective dopamine receptor agonist, on systemic and renal hemodynamics in normotensive subjects

Objective: Acute renal failure, frequently a consequence of renal vasoconst riction and subsequent renal ischemia, is a common problem for which no pro ven preventive or therapeutic agents exist. Fenoldopam is a new, selective, dopamine-1 receptor agonist that causes both systemic and renal arteriolar vasodilation. In hypertensive patients, fenoldopam rapidly decreases blood pressure, increases renal blood flow, and maintains or improves the glomer ular filtration rate. We sought to determine a dose of fenoldopam that incr eases renal blood flow without inducing hypotension in normotensive patient s and to explore the role of volume status (sodium replete vs, deplete) in these effects. Design: Randomized, double-blind, placebo-controlled, crossover study. Setting: Clinical research unit. Patients: Fourteen normal male volunteers, Interventions: Renal plasma Row (para-aminohippurate clearance) and glomerular filtration rate (inulin clea rance) were measured during three fixed, escalating doses of fenoldopam (0. 03, 0.1, and 0.3 mu g/kg/min) on both a high-sodium and a low-sodium diet. Measurements and Main Results: Fenoldopam significantly increased renal pla sma flow in a dose-dependent manner compared with placebo: 670 +/- 148 vs. 576 +/- 85 mL/min at 0.03 mu g/kg/min; 777 +/- 172 vs. 579 +/- 80 mL/min at 0.1 mu g/kg/min; and 784 +/- 170 vs. 592 +/- 165 mL/min at 0.3 mu g/kg/min (p < .05 fenoldopam vs. placebo at all three doses). Glomerular filtration rate was maintained. At the lowest dose (i.e., 0.03 mu g/kg/min), signific ant renal blood flow increases occurred without changes in systemic blood p ressure or heart rate. At 0.1 and 0.3 mu g/kg/min, systolic blood pressure did not change, but diastolic blood pressure was slightly lower in the feno ldopam group than in the placebo group: 62.5 +/- 6.4 vs. 63.6 +/- 2.6 mm Hg , respectively, at 0.3 mu g/kg/min (p < .05). None of the effects of fenold opam were altered by volume status. Conclusions: Fenoldopam increased renal blood how in a dose-dependent manne r compared with placebo, and, at the lowest dose, significantly increased r enal blood flow occurred without changes in systemic blood pressure or hear t rate. These findings will be useful in designing future studies exploring the role of fenoldopam in preventing or treating renal failure in patients who are not hypertensive.