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Document Details : Title: Hypotensive effect of dopamine Subtitle: Synergism induced by fenoldopam or levodopa Author(s): PRIETO, Juan Carlos , QUEVEDO, Mónica , MIRANDA, Hugo F. , PINARDI, Gianni Journal: Acta Cardiologica Volume: 60 Issue: 3 Date: June 2005 Pages: 253-257 DOI: 10.2143/AC.60.3.2005004 Abstract : Objective — 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. Methods and results — 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. Conclusions — The present results show that in the rat, after a-adrenergic blockade, the association of DA and FD could inappropriately potentiate the hypotension induced by both drugs. |
