Analysis of the cerebrovascular effects of 5-hydroxytryptamine in unanesthetized goats.

The effects of 5-hydroxytryptamine (5-HT, serotonin) on cerebral blood flow were evaluated in unanesthetized goats under normal conditions and after selective blockade of 5-HT receptors or impairment of the sympathetic activity present in cerebral vessels. Small doses of 5-HT (0.1-9 micrograms) injected directly into the internal maxillary artery produced dose-dependent reductions in cerebral blood flow, a decrease of 49.8 +/- 2.5% (S.E.M.) occurring with the highest dose. Slow i.v. infusion of lysergic acid diethylamide (0.2-0.4 micrograms/kg/min), methysergide or cyproheptadine (2-5 micrograms/kg/min) partially abolished the cerebral vasoconstriction produced by 5-HT. Both phentolamine and reserpine also diminished the vasoconstriction induced by 5-HT. Goats in which the superior cervical sympathetic ganglion had been removed 7 to 20 days before the experiment showed a significant decrease in the cerebral vasoconstriction elicited by 5-HT. These results indicate that 5-HT produces marked reduction in cerebral blood flow by direct excitatory effect on tryptaminergic receptors together with an indirect effect mediated by the uptake of 5-HT into the sympathetic nerve endings and the release of norepinephrine.