Hypotensive effect of dopamine: synergism induced by fenoldopam or levodopa

The effects of the co-administration of fenoldopam (FD) or levodopa (LD) with dopamine (DA) on arterial blood pressure were studied in rats to assess the possibility of synergic effects that might be of some clinical importance.

Mean arterial blood pressure (MBP) in the carotid artery of anaesthetized rats was registered. All agents induced dose-dependent reductions in mean arterial blood pressure when administered in a non-cumulative schedule to rats pretreated with phentolamine. For each drug, the doses that induced a 50% of reduction in basal mean arterial blood pressure, (ED50) calculated by standard linear regression analysis of the log dose-response curve and were 5.49 mg/kg, (n=10), 2.86 mg/kg, (n=11) and 0.445 mg/kg, (n=12), for FD, LD and DA, respectively. The interactions were evaluated by simultaneous administration of different fixed ratios of DA with FD (1:12.3) or DA with LD (1:6) and obtaining dose-response curves and ED50's for each mixture. An isobolographic analysis was then performed, which demonstrated that the co-administration had synergistic effects as illustrated by statistically higher reductions of blood pressure under each combination as compared to theoretical calculated additive effects.

The present results show that in the rat, after alpha-adrenergic blockade, the association of DA and FD could inappropriately potentiate the hypotension induced by both drugs.