VASOCONSTRICTOR RESPONSE INDUCED BY 5-HYDROXYTRYPTAMINE RELEASED FROM VASCULAR ADRENERGIC-NERVES BY PERIARTERIAL NERVE-STIMULATION

Abstract

The vasoconstrictor response to 5-hydroxytryptamine (5-HT) released from vascular adrenergic nerves by periarterial nerve stimulation (PNS) was studied in the perfused mesenteric vascular bed isolated from the rat. PNS was delivered at 4-16 Hz, 2 ms in pulse duration for 30 s. After treatment with 5-HT (1 and 10 .mu.M) for 20 min, the pressor response to PNS, previously decreased by 80-90% with phentolamine (0.1 .mu.M), was greatly potentiated and a frequency-dependent pressor response to PNS reappeared. The 5-HT treatment did not alter the pressor response to infusion of exogenous norepinephrine (0.5 and 1 nmol) previously decreased by phentolamine. This potentiation did not occur in the presence of methysergide (0.1 .mu.M), ketanserin (0.1 .mu.M), tetrodotoxin (0.1 .mu.M), guanethidine (5 .mu.M) or in Ca2+-free Krebs'' solution. In the preparation treated with 6-hydroxydopamine, 5-HT treatment had no effect on the abolished PNS response. Either cocaine (10 .mu.M) or fluoxetine (10 .mu.M) but not corticosterone (10 .mu.M) prevented the potentiation when perfused together with 5-HT. In the mesenteric vascualr bed prelabeled with [3H]-5HT, PNS evoked a frequency-dependent increase of tritium efflux, which was abolished by treatment with tetrodotoxin, guanethidine or 6-hydroxydopamine and in Ca2+-free Krebs'' solution. 5-HT is apparently taken up by vascular adrenergic nerve endings in vitro and is released by nerve stimulation, resulting in vasoconstriction. 5-HT may contribute to the maintenance of local vascular tone through this mechanism in vivo.