Inhibition of serotonin-induced increase in canine external carotid blood flow by drugs that decrease the sympathetic outflow.

1. The present study was designed to analyse the effect of the centrally-acting sympatho-inhibitory drugs, prazosin and ketanserin, on the increase in external carotid blood flow (external CBF) produced by 5-hydroxytryptamine (5-HT) in pentobarbital-anaesthetized dogs. 2. Intracarotid (i.c.) infusions of 5-HT (10 micrograms min-1 during 1 min) produced an increase in external CBF without changes in mean arterial blood pressure or heart rate. This response to 5-HT was dose-dependently blocked by intravenous (i.v.) administration of prazosin (1, 3, 10, 30 and 100 micrograms kg-1) or ketanserin (10, 30, 100 and 300 micrograms kg-1). 3. Furthermore, 5-HT-induced increase in external CBF was inhibited by either the ganglionic blocking agent, mecamylamine (0.03, 0.1, 0.3, 1, 3 and 10 mg kg-1), the mixed 5-HT1-like and 5-HT2 receptor antagonist, methiothepin (3, 10 and 30 micrograms kg-1) or the 5-HT1A ligand, spiroxatrine (10, 30, 100 and 300 micrograms kg-1). In contrast, the selective 5-HT2 and 5-HT1C receptor antagonist, ritanserin (30 and 100 micrograms kg-1, i.v.), was unable to block the above response to 5-HT. 4. It is concluded that the inhibition of 5-HT-induced increase in external CBF by prazosin, ketanserin, mecamylamine and spiroxatrine is due to a reduction in the sympathetic tone and not to a blockade of 5-HT receptors.