Pharmacological identification of the major subtypes of adrenoceptors involved in the canine external carotid vasoconstrictor effects of adrenaline and noradrenaline.
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 (alpha1) and BHT933 (6-Ethyl-5,6,7,8-tetrahydro-4H-oxazolo [4,5-d] azepin-2-amine dihydrochloride; alpha2); (ii) abolished after phentolamine (2000 microg/kg) unmasking a vasodilator component (subsequently blocked by propranolol; 1000 microg/kg); and (iii) partly blocked by rauwolscine (30 and 100 microg/kg), and subsequently abolished by prazosin (100 microg/kg). Accordingly, rauwolscine (100 and 300 microg/kg) markedly blocked the responses to BHT933 without affecting those to phenylephrine; likewise, prazosin (100 microg/kg) markedly blocked the responses to phenylephrine without affecting those to BHT933. These results show that both alpha1- and alpha2-adrenoceptors mediate vasoconstriction within the canine external carotid circulation. Moreover, after blockade of alpha1/alpha2-adrenoceptors, both adrenaline and noradrenaline exhibit a beta-adrenoceptor-mediated vasodilator component.
Willems
E W
EW
Pharmacology, Erasmus University, Rotterdam, The Netherlands.
Valdivia
L F
LF
Ramírez-San Juan
E
E
Saxena
P R
PR
Villalón
C M
CM
D000322:Adrenergic Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002342:Carotid Artery, External / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D013562:Sympathectomy; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
D000322:Adrenergic Agonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D001381:Azepines; D020033:Protein Isoforms; D011941:Receptors, Adrenergic; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D015016:Yohimbine; D011433:Propranolol; C015603:azepexole; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine; D010646:Phentolamine