Vasoconstrictor response induced by 5-hydroxytryptamine released from vascular adrenergic nerves by periarterial nerve stimulation.
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 to 16 Hz, 2 msec in pulse duration for 30 sec. After treatment with 5-HT (1 and 10 microM) for 20 min, the pressor response to PNS, previously decreased by 80 to 90% with phentolamine (0.1 microM), was greatly potentiated and a frequency-dependent pressor response to PNS reappeared. However, 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 microM), ketanserin (0.1 microM), tetrodotoxin (0.1 microM), guanethidine (5 microM) or in Ca++-free Krebs' solution. Also, in the preparation treated with 6-hydroxydopamine, 5-HT treatment had no effect on the abolished PNS response. Either cocaine (10 microM) or fluoxetine (10 microM) but not corticosterone (10 microM) prevented the potentiation when perfused together with 5-HT. In the mesenteric vascular bed prelabeled with [3H]-5-HT, PNS evoked a frequency-dependent increase of tritium efflux, which was abolished by treatment with tetrodotoxin guanethidine or 6-hydroxydopamine and in Ca++-free Krebs' solution. These results suggest that 5-HT is taken up by vascular adrenergic nerve endings in vitro and it is released by nerve stimulation, resulting in vasoconstriction. It is also suggested that 5-HT may contribute to the maintenance of local vascular tone through this mechanism in vivo.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D005473:Fluoxetine / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D016627:Oxidopamine; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D006892:Hydroxydopamines; D005473:Fluoxetine; D012701:Serotonin; D016627:Oxidopamine; D003042:Cocaine; D009638:Norepinephrine; D010646:Phentolamine