title: Pharmacological evidence that alpha1-and alpha2-adrenoceptors mediate vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs.
abstract: Vasoconstriction of carotid arteriovenous anastomoses may be involved in the therapeutic action of acutely acting anti-migraine 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 alpha1- and alpha2-adrenoceptors in mediating vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs. Ten minute intracarotid infusions of phenylephrine (1, 3 and 10 microg kg(-1) min(-1)) or BHT 933 (3, 10 and 30 microg kg(-1) min(-1)) produced dose-dependent decreases in total carotid and arteriovenous anastomotic conductances; no changes were observed in the capillary fraction. The carotid vascular effects of phenylephrine and BHT 933 were selectively abolished by prazosin (100 microg kg(-1), i.v.) and rauwolscine (300 microg 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 microg kg(-1), i.v.). These results show that both alpha1- and alpha2-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 alpha2-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 anti-migraine agents and may eventually be helpful in the development of future treatment in migraine.
authors.affiliation: Department of Pharmacology, Dutch Migraine Research Group and Cardiovascular Research Institute COEUR, Erasmus University Medical Centre Rotterdam, The Netherlands.
authors.forename: E W
authors.initials: EW
authors.lastname: Willems
authors.forename: M
authors.initials: M
authors.lastname: Trion
authors.forename: P
authors.initials: P
authors.lastname: De Vries
authors.forename: J P
authors.initials: JP
authors.lastname: Heiligers
authors.forename: C M
authors.initials: CM
authors.lastname: Villalón
authors.forename: P R
authors.initials: PR
authors.lastname: Saxena
mesh_terms: D000758:Anesthesia; D000818:Animals; D001163:Arteriovenous Anastomosis / Q000187:drug effects* / Q000502:physiology; D001381:Azepines / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D008881:Migraine Disorders / Q000188:drug therapy; D010069:Oxadiazoles / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology; D018170:Sumatriptan / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D001381:Azepines; D010069:Oxadiazoles; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D011985:Receptors, Serotonin; D010656:Phenylephrine; C090701:GR 127935; D018170:Sumatriptan; C015603:azepexole; D011224:Prazosin