Serotonin-induced vasoconstriction in rabbit femoral artery: mediation by both 5-HT2 serotonergic and alpha 1-adrenoceptors

We determined the receptors mediating the contractile response of the rabbit femoral artery to serotonin in isolated vascular rings mounted in tissue baths for the measurement of isometric contraction. Serotonin elicited a biphasic concentration-response curve (CRC). The threshold and maximal concentrations of the first phase were 0.03 and 3 microM, respectively. The respective values for the second phase were 10 and 1,000 microM. Benextramine, a selective, irreversible alpha-adrenoceptor antagonist, eliminated the second phase. Similar results were obtained with benextramine in femoral arteries acutely denervated with 6-hydroxydopamine (6-OHDA). In contrast, the reversible, competitive 5-HT2 antagonist ketanserin shifted the first phase of the serotonin CRC to the right ina concentration-dependent manner but had little or no effect on the second phase. No evidence for functional alpha 2-adrenoceptors was found. We conclude that the first phase of the serotonin CRC in rabbit femoral artery was mediated predominantly by 5-HT2 receptors and that the second phase was mediated by alpha 1-adrenoceptors.