ROLE OF ALPHA(1)-ADRENOCEPTORS IN THE REDUCTION OF EXTERNAL CAROTID BLOOD-FLOW INDUCED BY BUSPIRONE AND IPSAPIRONE IN THE DOG

The effects of the 5-HT1A receptor agonists with anxiolytic properties , buspirone and ipsapirone, in the external carotid bed of anaesthetiz ed dogs were analyzed. Since these agonists produce several vascular e ffects via activation of both 5-HT receptors and alpha(1)-adrenoceptor s, their effects were compared with those elicited by the 5-HT agonist , quipazine, and the alpha(1)-adrenoceptor agonist, methoxamine. 1-Min intracarotid (i.c.) infusions of buspirone (300 mu g/min), ipsapirone (40 mu g/min), quipazine (300 mu g/min) and methoxamine (15 mu g/min) produced consistent decreases in external carotid blood flow (ECBF); since these changes in blood flow were not accompanied by modification s in systemic blood pressure, the agonists produced parallel increases in external carotid resistance. After interruption of the sympathetic tone by bilateral cervical vagosympathectomy, the vasoconstrictor res ponses to all the agonists remained unaffected. The intravenous (i.v.) administration of the nonselective 5-HT1-like receptor antagonist, me thiothepin (1-100 mu g/kg), potently and dose-dependently antagonized buspirone-, ipsapirone- and quipazine-induced vasoconstriction; methio thepin similarly antagonized the vasoconstrictor responses to methoxam ine. Interestingly, the alpha(1)-adrenoceptor antagonist, prazosin (1- 100 mu g/kg, i.v.), also antagonized the vasoconstrictor responses to buspirone, ipsapirone and methoxamine in a dose-dependent manner. Fina lly, buspirone (300 mu g/min, i.c.) and ipsapirone (40 mu g/min, i.c.) did not modify the responses to noradrenaline (10 mu g/min, i.c.) or tyramine (100 mu g/min, i.c.). It is concluded that canine external ca rotid vasoconstriction induced by buspirone and ipsapirone is mainly m ediated by activation of alpha(1)-adrenoceptors located in vascular sm ooth muscle, These data further highlight the ability of the above anx iolytics to produce significant vascular effects under in vivo conditi ons.