Mathur VS. Swan SK. Lambrecht LJ. Anjum S. Fellmann J. McGuire D. Epstein M. Luther RR. The effects of fenoldopam, a selective dopamine receptor agonist, on systemic and renal hemodynamics in normotensive subjects Critical Care Medicine. 27(9):1832-7, 1999.
Summary
Acute renal failure, frequently a consequence of renal vasoconstriction and subsequent renal ischemia, is a common problem for which no proven preventive or therapeutic agents exist. Fenoldopam, a selective dopamine-1 receptor agonist that causes both systemic and renal arteriolar vasodilation, decreases blood pressure, increases renal blood flow, and maintains or improves the glomerular filtration rate in hypertensive patients. The authors studied doses of fenoldopam that increase renal blood flow without inducing hypotension in normotensive volunteers; and explored the role of volume status (sodium replete vs. deplete) in producing these effects. In a randomized, double-blind, placebo-controlled, cross-over study in a clinical research unit, 14 normal male volunteers were studied. Renal plasma flow (para-aminohippurate clearance) and glomerular filtration rate (inulin clearance) were measured during three fixed, escalating doses of fenoldopam (0.03, 0.1, and 0.3 mcg/kg/min) on both a high-sodium and a low-sodium diet. The authors found that fenoldopam significantly increased renal plasma flow in a dose-dependent manner compared with placebo: 670 +/- 148 vs. 576 +/- 85 mUmin at 0.03 mcg/kg/min; 777 +/- 172 vs. 579 +/- 80 mUmin at 0.1 mcg/kg/min; and 784 +/- 170 vs. 592 +/- 165 mUmin at 0.3 mcg/kg/min (p < .05 fenoldopam vs. placebo at all three doses). Glomerular filtration rate was maintained. At the lowest dose (i.e., 0.03 mcg/kg/min), significant renal blood flow increases occurred without changes in systemic blood pressure or heart rate. At 0.1 and 0.3 mcg/kg/ min, systolic blood pressure did not change, but diastolic blood pressure was slightly lower in the fenoldopam group than in the placebo group: 62.5 +/- 6.4 vs. 63.6 +/- 2.6 mm Hg, respectively, at 0.3 mcg/kg/min (p < .05). None of the effects of fenoldopam were altered by volume status. The authors conclude that fenoldopam increased renal blood flow in a dose-dependent manner compared with placebo, and, at the lowest dose, significantly increased renal blood flow occurred without changes in systemic blood pressure or heart 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.