Relative DA1-Dopamine-Receptor Agonist and α-Adrenoceptor Antagonist Activity of Fenoldopam in the Anesthetized Dog

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Abstract
Relative DA1-dopamine-receptor agonist and .alpha.-adrenoceptor antagonist activities of fenoldopam were determined in pentobarbital anesthetized dogs. The renal vasodilating effect of intravenous infusions of fenoldopam was used as an index of its DA1-agonist activity. Inhibition by fenoldopam of femoral vasoconstriction produced by intraarterial administration of phenylephrine (a relatively selective .alpha.1 agonist) and UK 14,304 (a relatively selective .alpha.2 agonist) was used to determine its .alpha.-adrenoceptor antagonist activity. Intravenous infusions of 0.1 and 0.2 .mu.g/kg/min of fenoldopam caused dose-related reductions in renal vascular resistance and mean arterial pressure. Higher rates of infusions of fenoldopam (2 and 5 .mu.g/kg/min) were given after pretreatment with 50 .mu.g/kg SCH 23390 (a DA1-selective antagonist) to attenuate DA1-mediated hemodynamic effects. After SCH 23390, the infusion of 5 .mu.g/kg/min of fenoldopam produced approximately the same hypotensive and renal vasodilating actions as the 0.2 .mu.g/kg/min infusion without SCH 23390. Alpha-adrenoceptor blocking activity was not observed with the 0.1. 0.2, and 2 .mu.g/kg/min infusions of fenoldopam. The 5 .mu.g/kg/min infusion, however, produced 14 and 25% inhibition of the vasoconstrictor effects of phenylephrine and UK 14,304, resepctively. These data indicate that fenoldopam decreases renal vascular resistance in doses which are 25 to 50 times less than the dose needed to antagonize .alpha. adrenoceptors.