Beta 1-adrenoceptor antagonism by urapidil prior to and after the alpha 2-antagonist rauwolscine in anesthetized dogs.
The purpose of this investigation was to evaluate the in vivo beta-adrenoceptor antagonistic properties of urapidil, a new antihypertensive alpha 1-adrenoceptor blocking agent. In dogs anesthetized with pentobarbital, the cardioaccelerator nerve was isolated, decentralized and stimulated electrically to elicit adrenergically mediated increases in heart rate. Dobutamine was administered (3-30 micrograms/kg i.v.) to elicit increases in heart rate by the direct stimulation of beta-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 alpha 2-antagonist rauwolscine was administered (1000 micrograms/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 beta 1-blocking activity more clearly seen after blockade of alpha 2-adrenoceptors.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014628:Vagotomy; D015016:Yohimbine / Q000494:pharmacology*
D006584:Hexamethonium Compounds; D010879:Piperazines; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; D004280:Dobutamine; D011433:Propranolol; C015568:urapidil