β1-adrenoceptor antagonism by urapidil prior to and after the α2-antagonist rauwolscine in anesthetized dogs

Abstract The purpose of this investigation was to evaluate the in vivo β-adrenoceptor antagonistic properties of urapidil, a new antihypertensive α 1 -adrenoceptor blocking agent. In dogs anesthetized with pentobarbital, the cardioaccelator nerve was isolated, decentralized and stimulated electrically to elicit adrenergically mediated increases in heart rate. Dobutamine was administered (3–30 μg/kg i.v.) to elicit increases in heart rate by the direct stimulation of β-adrenoceptors. Urapidil 2 mg/kg i.v. had no significant effect on cardioaccelerator nerve-induced tachycardia, but 5 mg/kg i.v. decreased the response by 27%. Heart rate responses to dobutamine were suppressed slightly by the low dose of urapidil and to a greater degree by the high dose of urapidil, whereas the pressor response to dobutamine was markedly attenuated at both dose levels. Neurally or dobutamine-elicited tachycardia remaining after urapidil treatment was eliminated by propranolol (1 mg/kg i.v.). When the selective α 2 -antagonist rauwolscine was administered (1000 μg/kg i.v.), tachycardic responses to nerve stimulation increased 49% above control, and urapidil (5 mg/kg) given subsequently, caused a 48% reduction in the response. These data indicate that urapidil has weak β 1 -blocking activity more clearly seen after blockade of α 2 -adrenoceptors.