Pharmacological evidence that α1- and α2-adrenoceptors mediate vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs

1 Vasoconstriction of carotid arteriovenous anastomoses may be involved in the therapeutic action of acutely acting antimigraine agents, including the triptans and ergot alkaloids. While 5-HT1B/1D receptors mediate the effect of triptans, ergotamine and dihydroergotamine also interact with alpha-adrenoceptors. In the present study, we investigated the potential role of alpha(1)- and alpha(2)-adrenoceptors in mediating vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs. 2 Ten minute intracarotid infusions of phenylephrine (1, 3 and 10 mu g kg(-1) min(-1)) or BHT 933 (3, 10 and 30 mu g kg(-1) min(-1)) produced dose-dependent decreases in total carotid and arteriovenous anastomotic conductances; no changes were observed in the capillary fraction. 3 The carotid Vascular effects of phenylephrine and BHT 933 were selectively abolished by prazosin (100 mu g kg(-1), i.v.) and rauwolscine (300 mu g kg(-1), i.v.), respectively. The responses to phenylephrine and BHT 933 were not affected by the selective 5-HT1B/1D receptor antagonist GR127935 (500 mu g kg-L, i.v.). 4 These results show that both alpha(1)- and alpha(2)-adrenoceptors can mediate vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs. Since vasoconstrictor activity in this in vivo model is predictive of anti-migraine activity, an agonist activity at particularly the alpha(2)-adrenoceptor subtypes, in view of their less ubiquitous nature, could provide migraine abortive potential. Thus, the present results may aid further understanding of the mode of action of some current antimigraine agents and may eventually be helpful in the development of future treatment in migraine.