Noradrenergic component in the vasoconstriction induced by 5-hydroxytryptamine in goat cerebral arteries

Abstract

5-Hydroxytryptamine (5-HT) elicited dose-dependent increases in tension in the middle cerebral artery of the goat, which were significantly antagonized by lysergic acid diethylamide (LSD, 10(-8) M) and methysergide (10(-7) M). In the presence of phentolamine (10(-6) M), the dose-response curve to 5-HT was shifted to the right, the pA2 value for this antagonism was 6.52. Pretreatment of goats with reserpine (0.02 mg kg-1 day-1 for three days) or removal of both superior cervical ganglia 15 days before the experiment brought about a significant decrease in the vasoconstriction induced by doses of 5-HT higher than 10(-7) M. The remaining contraction produced by 5-HT in arterial segments from reserpinized or gangliectomized goats was further reduced in the presence of LSD. In addition, high concentrations of 5-HT induced tritium release from goat pial arteries preloaded with (-)-[3H]noradrenaline, 2 X 10(-7) M) which was significantly decreased in vessels from gangliectomized or reserpinized goats. These results in goat cerebral arteries indicate that in the contraction evoked by 5-HT there are two components. The first appears with low concentrations (up to 10(-7) M) in which 5-HT acts directly on 5-HT receptors. The second occurs at high doses (greater than 10(-7) M) in which 5-HT also acts indirectly on alpha-adrenoceptors by release of noradrenaline from noradrenergic nerve endings.