5-Hydroxytryptamine delays relaxation time of norepinephrine-induced vasoconstriction

The effect of low concentration of 5-hydroxytryptamine (5-HT; 0.03-0.3 microM) on cellular and extracellular Ca2+ -dependent norepinephrine (NE; 5 microM)-induced vasoconstriction was assessed in isolated perfused rabbit ear artery. The most remarkable effect of 5-HT is a concentration-dependent enhancement of the duration of the extracellular Ca2+ -dependent NE-induced vasoconstriction. This effect of 5-HT is still present in 6-hydroxydopamine-pretreated arteries and in the presence of deoxycorticosterone and is not mimicked by the K+ channel blocker tetraethylammonium. Administration of nifedipine (0.3 microM) and EDTA (1 mM) failed to antagonize 5-HT-induced prolongation of relaxation kinetics of extracellular Ca2+ -dependent NE-induced vasoconstriction. On the other hand, this phenomenon was abolished by caffeine (15 mM) and markedly reduced by dibutyryl cyclic AMP (3 mM). 5-HT (0.3 microM), but not NE (30-50 nM), enhanced the vasoconstriction elicited by caffeine (15 mM) that was procaine sensitive and unaffected by nifedipine. These results suggest that 5-HT prolonged relaxation kinetics of NE-induced vasoconstriction through an impairment of cellular mechanisms that decrease the myoplasmic level of free Ca2+. A similar mechanism could be of relevance for 5-HT enhancement of vascular smooth muscle responsiveness to vasoactive agents.