Relaxant effect of nitric oxide and prostacyclin on serotonin‐induced vasocontraction of human umbilical artery

BACKGROUND: We investigated the effect of nitric oxide and prostacyclin, which are endothelium-derived vasodilators, on serotonin (5-HT)-induced vasocontraction, and 5-HT1-serotoninergic receptor mediated relaxation in the human umbilical artery. METHODS: Serotonin-stimulated vasocontraction was measured in umbilical artery segments treated with and without 1) L-arginine (10(-4) M approximately 10(-2) M), a precursor of nitric oxide synthesis; 2) methylene blue (10(-5) M) and L-NG-monomethyl arginine (LNMA, 2 X 1O(-4) M), which are specific inhibitors of nitric oxide action and nitric oxide synthesis, respectively; and 3) tranylcypromine (2 X 10(-6) M, 2 X 10(-5) M), an inhibitor of prostacyclin synthesis. 4) Vessels were pretreated with M1, an inhibitor of 5-HT2 serotoninergic receptors, and then prostaglandin F2 alpha (9.O X 1O(-7) M). Finally, we measured the 5-HT1, receptor-mediated relaxation induced by 5-HT. RESULTS: Treatment with L-arginine significantly inhibits 5-HT-induced contraction in a dose-dependent manner. Treatment with methylene blue and LNMA significantly potentiated 5-HT-induced contraction. Tranylcypromine caused no significant changes in 5-HT-induced vasocontraction. 5-HT1 serotoninetic receptor-mediated relaxation was found at higher concentrations of 5-HT (greater than 4.94 X 10(-5) M). CONCLUSIONS: Our results suggest that nitric oxide may exert a strong relaxant effect on 5-HT-induced vasocontraction compared with prostacyclin in human umbilical artery.