5-HT1B receptors, α2A/2C- and, to a lesser extent, α1-adrenoceptors mediate the external carotid vasoconstriction to ergotamine in vagosympathectomised dogs

It has previously been suggested that ergotamine produces external carotid vasoconstriction in vagosympathectomised dogs via 5-HT1B/1D receptors and alpha(2)-adrenoceptors. The present study has reanalysed this suggestion by using more selective antagonists alone and in combination. Fifty-two anaesthetised dogs were prepared for ultrasonic measurements of external carotid blood flow. The animals were divided into thirteen groups (n=4 each) receiving an i.v. bolus injection of, either physiological saline (0.3 ml/kg; control), or the antagonists SB224289 (300 mug/kg; 5-HT1B), BRL15572 (300 mug/kg; 5-HT1D), rauwolscine (300 mug/kg; alpha(2)), SB224289 + BRL15572 (300 mug/kg each), SB224289 + rauwolscine (300 mug/kg each), BRL15572 + rauwolscine (300 mug/kg each), rauwolscine (300 mug/kg) + prazosin (100 mug/kg; alpha(1)), SB224289 (300 mug/kg) + prazosin (100 mug/kg), SB224289 (300 mug/kg) + rauwolscine (300 mug/kg) + prazosin (100 mug/kg), SB224289 (300 mug/kg) + prazosin (100 mug/kg) + BRL44408 (1,000 mug/kg; alpha(2A)), SB224289 (300 mug/kg) + prazosin (100 mug/kg)+ imiloxan (1,000 mug/kg; alpha(2B)), or SB224289 (300 mug/kg) + prazosin (100 mug/kg) + MK912 (300 mug/kg; alpha(2C)). Each group received consecutive 1-min intracarotid infusions of ergotamine (0.56, 1, 1.8, 3.1, 5.6, 10 and 18 mug/min), following a cumulative schedule. In saline-pretreated animals, ergotamine induced dose-dependent decreases in external carotid blood flow without affecting arterial blood pressure or heart rate. These control responses were: unaffected by SB224289, BRL15572, rauwolscine or the combinations of SB224289 + BRL15572, BRL15572 + rauwolscine, rauwolscine + prazosin, SB224289 + prazosin, or SB224289 + prazosin + imiloxan; slightly blocked by SB224289 + rauwolscine; and markedly blocked by SB224289 + rauwolscine + prazosin, SB224289 + prazosin + BRL44408 or SB224289 + prazosin + MK912. Thus, the cranio-selective vasoconstriction elicited by ergotamine in dogs is predominantly mediated by 5-HT1B receptors as well as alpha(2A/2C)-adrenoceptor subtypes and, to a lesser extent, by alpha(1)-adrenoceptors.