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.
D000818:Animals; D001158:Arteries / Q000166:cytology / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D004347:Drug Interactions; D004423:Ear / Q000098:blood supply; D004492:Edetic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology*; D012965:Sodium Chloride / Q000494:pharmacology; D013563:Sympathectomy, Chemical; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D013757:Tetraethylammonium Compounds; D012701:Serotonin; D002110:Caffeine; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D003994:Bucladesine; D019789:Tetraethylammonium; D004492:Edetic Acid; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine