An amplifying effect of exogenous and neurally stored 5‐hydroxytryptamine on the neurogenic contraction in rat tail artery

1 The interactions between sympathetic neuroeffector transmission and 5‐hydroxytryptamine (5‐HT) were investigated in segments of rat isolated tail artery. 2 Contractile responses to field stimulation of the artery segments were abolished by tetrodotoxin (3 × 10 −7 m ). A subthreshold concentration of acutely applied exogenous 5‐HT (10 −8 m ) markedly enhanced the contractions induced by sympathetic nerve stimulation, through an action on postjunctional 5‐HT 2 ‐receptors. 3 The amplifying effect of 5‐HT involved an enhanced influx of extracellular calcium into the smooth muscle cells. In contrast, the neurogenic contractions in vessels not exposed to 5‐HT were not dependent on extracellular calcium. 4 The adrenergic component of the amplified response involved postjunctional α 1 ‐ but not α 2 ‐ adrenoceptor activation. 5 Exposure of the vessels to 5‐HT (5 × 10 −7 m ) for 30 min resulted in uptake of the amine into the perivascular sympathetic nerves, as demonstrated by immunohistochemistry. After chemical sympathectomy with 6‐hydroxydopamine in vitro or in vivo , or surgical sympathectomy, there was little or no uptake. 6 Exposure to 5‐HT followed by repeated washing resulted in an enhancement of the neurogenic contraction, which was still fully tetrodotoxin‐sensitive. The enhanced response was blocked by ketanserin (10 −8 m ) and prevented by the presence of the 5‐HT uptake blocker, paroxetine (3 × 10 −8 m ), during the period of exposure to 5‐HT.