The role of alpha-adrenoceptor blockade in the antihypertensive effects of fenoldopam in humans.

Fenoldopam, a dopamine-1 receptor agonist, has been reported to exhibit alpha-adrenoceptor-blocking actions in intact and isolated animal preparations. To determine whether alpha-adrenoceptor blockade contributes to its antihypertensive properties in humans, the effects of fenoldopam on the pressor responses to norepinephrine and angiotensin II were compared in eight normal volunteers. Fenoldopam (0.5 micrograms/kg/min) shifted the dose-response curves for both agonists to the right (p less than 0.05). Dose ratios for an increase in mean blood pressure of 10 mm Hg were 3.3 +/- 0.9 for norepinephrine and 3.2 +/- 0.6 for angiotensin II (p not significant). Consequently, fenoldopam is not a selective alpha-adrenoceptor antagonist at therapeutic concentrations in humans.