Paradoxical inotropic effects of clonidine and labetalol in the conscious rabbit

Both 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 beta-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 microgram/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 alpha-adrenoceptor-agonist properties which both drugs possess and which could be unmasked by cardiac autonomic blockade.