5-Hydroxytryptamine Induces Vasoconstriction of the Human Umbilical Artery: Effects of Hypoxia and Nicorandil

Abstract

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% O₂–5% CO₂ in N₂). 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.

Metabolic Dysregulation Contributes to the Progression of Alzheimer’s Disease

“…Thus, both pimavanserin and citalopram increase the concentration of 5-HT in the synaptic cleft. Tiritilli (2000) found that oxygen deficit and glucose deprivation inhibit the contractive response of umbilical arteries to 5-HT, which implies that aerobic glycolysis can increase sensitivity to 5-HT. Research into human pancreatic ductal adenocarcinoma also indicates that the levels of enzymes participating in glycolysis increase after 5-HT stimulation (Jiang et al, 2017).…”

Novel insights for the role of nitric oxide in placental vascular function during and beyond pregnancy

“…In this regard, further studies focus on chorionic and umbilical arteries are required to enhance the understanding of the placental vascular function and dysfunction, especially considering their specific responses to oxygen (Hampl & Jakoubek, 2009), shear stress (Hoffmann et al, 2003;Learmont & Poston, 1996;Saw et al, 2018), and oxidative stress (Proietti et al, 2016). Moreover, there are significant differences within the arterial vascular bed in the placenta, especially those related to the vasoconstriction to diverse oxygen levels (Hampl & Jakoubek, 2009;Leung et al, 2006;Tiritilli, 2000).…”

How is the human umbilical artery regulated?

“…The HUA contraction depends entirely on vasoactive substances released locally or existing in the circulation, such as 5-HT, [31][32][33][34][35][36] His, [35][36][37][38] thromboxane, 14,35 bradykinin, 35,39,40 endothelin 1 35,41,42 and prostaglandin F2α (PGF2α) 43 (Fig. 2).…”