Pharmacological evidence that alpha(1)- and alpha(2)-adrenoceptors mediatevasoconstriction 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-adr enoceptors. In the present study, we investigated the potential role of alp ha(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-dep endent decreases in total carotid and arteriovenous anastomotic conductance s; no changes were observed in the capillary fraction. 3 The carotid Vascular effects of phenylephrine and BHT 933 were selectivel y abolished by prazosin (100 mu g kg(-1), i.v.) and rauwolscine (300 mu g k g(-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 med iate vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs. Since vasoconstrictor activity in this in vivo model is predictive o f anti-migraine activity, an agonist activity at particularly the alpha(2)- adrenoceptor subtypes, in view of their less ubiquitous nature, could provi de migraine abortive potential. Thus, the present results may aid further u nderstanding of the mode of action of some current antimigraine agents and may eventually be helpful in the development of future treatment in migrain e.