Pharmacological identification of the major subtypes of adrenoceptors involved in the canine external carotid vasoconstrictor effects of adrenaline and noradrenaline

Abstract

This study investigated the potential effects of adrenaline and noradrenaline on the external carotid blood flow of vagosympathectomised dogs and the receptor mechanisms involved. One minute (1 min) intracarotid infusions of adrenaline and noradrenaline produced dose-dependent decreases in external carotid blood flow without changes in blood pressure or heart rate. These responses, which remained unaffected after saline, were: ( i) mimicked by the adrenoceptor agonists, phenylephrine (α 1) and BHT933 (6-Ethyl- 5,6,7,8- tetrahydro- 4H- oxazolo [4,5-d] azepin-2-amine dihydrochloride; α 2); ( ii) abolished after phentolamine (2000 μg/kg) unmasking a vasodilator component (subsequently blocked by propranolol; 1000 μg/kg); and ( iii) partly blocked by rauwolscine (30 and 100 μg/kg), and subsequently abolished by prazosin (100 μg/kg). Accordingly, rauwolscine (100 and 300 μg/kg) markedly blocked the responses to BHT933 without affecting those to phenylephrine; likewise, prazosin (100 μg/kg) markedly blocked the responses to phenylephrine without affecting those to BHT933. These results show that both α 1- and α 2-adrenoceptors mediate vasoconstriction within the canine external carotid circulation. Moreover, after blockade of α 1/α 2-adrenoceptors, both adrenaline and noradrenaline exhibit a β-adrenoceptor-mediated vasodilator component.