Paradoxical Inotropic Effects of Clonidine and Labetalol in the Conscious Rabbit

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SummaryBoth clonidine and labetalol when given by bolus intravenous injection into conscious rabbits produce an initial rise in left ventricular pressure associated with a decrease in myocardial contractility as assessed by left ventricular dP/dt. While clonidine also produces a marked bradycardiac effect, labetalol causes no change in heart rate. Acute β-adrenoceptor blockade with propranolol, 1 mg/kg, i.v., does not significantly modify the response produced by either clonidine or labetalol. Following cardiac cholinergic blockade with scopolamine methylbromide, 50 μg/kg, the negative inotropic effect produced by clonidine is abolished and is replaced by a positive inotropic effect, while the negative inotropic response produced by labetalol is attenuated. Following cardiac autonomic blockade with propranolol and scopolamine methyl-bromide, both clonidine and labetalol produce a positive inotropic response. These positive inotropic responses may be due to the partial α-adrenoceptor-agonist properties which both drugs possess and which could be unmasked by cardiac autonomic blockade.

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