5-hydroxytryptamine induces vasoconstriction of the human umbilical artery: effects of hypoxia and nicorandil.

Human umbilical arteries are known to be modulated by oxygen partial pressure. To further understand the underlying mechanisms, rings were suspended in organ chambers for the measurement of isometric force. The effects of 5-hydroxytryptamine (10(-9) to 10(-5) M) were first investigated before and after hypoxic conditions (5% O(2)-5% CO(2) in N(2)). Then after pretreatment, we tested indomethacin (10(-5) M), N-nitro-L-arginine (L-NNA, 10(-5) M) and nicorandil (10(-5) M) each separately, then each of the three substances together with hypoxia. In separate experiments the contractions to 5-hydroxytryptamine (10(-9) to 10(-5) M) were effectuated in a glucose-free medium, and mitochondrial respiration was inhibited by cyanide (2 mM). Hypoxic conditions significantly reduced the contractive response to 5-hydroxytryptamine. Contractions were enhanced after indomethacin, but remained unchanged after L-NNA. Pretreatment with nicorandil decreased the contraction. Furthermore, hypoxia and nicorandil dramatically decreased the contraction to 5-hydroxytryptamine. In glucose-free medium under normoxia or in hypoxic conditions, 5-hydroxytryptamine did not induce any contraction. Moreover, cyanide (2 mM) remained without effect on the contraction obtained by 5-hydroxytryptamine. These results suggest that hypoxia and nicorandil attenuate vasoconstrictor responses to 5-hydroxytryptamine in human umbilical arteries. Furthermore, these findings suggest that prostacyclin acts as a functional antagonist to vasoconstriction whereas nitric oxide does not. Finally, glycolysis seems to be involved rather than mitochondrial metabolism.