How is the human umbilical artery regulated?

Abstract

The purpose of this review is to present an update of the main mechanisms involved in the physiological regulation of contraction and relaxation of the human umbilical artery (HUA) smooth muscle cells. A literature review was performed based on the analysis of papers available on PubMed. The most important and relevant studies regarding the regulation of the HUA are presented in this article. The vascular smooth muscle is a highly specialized structure, whose main function is to regulate the vascular tonus. This is controlled by a balance between the cellular signaling pathways that mediate contraction and relaxation. The cells responsible for the contractile property of this muscle are the smooth muscle cells (SMC), and an excellent source of these cells is the HUA, involved in fetoplacental circulation. Since the umbilical blood vessels are not innervated, the HUA tonus is modulated by vasoactive substances that regulate the contractile process. The main vasoactive substances that induce contraction are serotonin, histamine, thromboxane, bradykinin, endothelin 1 and prostaglandin F2α, that are linked to the activation of proteins G and G . On the other hand, the main vasorelaxation mechanisms are the activation of adenyl and guanil cyclases, potassium channels and the inhibition of calcium channels. The SMC from the HUA allow the study of different cellular mechanisms and their functions. Therefore, these cells are an important tool to study the mechanisms regulating the contractility of this artery, allowing to detect potential therapeutic targets to treat HUA disorders (gestational hypertension and pre-eclampsia).

Relaxant Effect of Monoterpene (−)-Carveol on Isolated Human Umbilical Cord Arteries and the Involvement of Ion Channels

“…They all act on the vasculature through their involvement with L-type Ca 2+ channels. In addition, the data obtained from (−)-carveol in the presence of elevated K + also support this evidence, since the contraction induced by potassium chloride (KCl) is mainly due to the influx of extracellular Ca 2+ through VOCCs, where this effect is partially inhibited by specific L-type Ca 2+ channel antagonists (LTCC) [26].…”

“…Elevation of [Ca 2+ ] i can also occur through the binding of external agonists such as 5-HT or His, including others, which trigger a signaling mechanism involving the activation of a complex cascade of secondary messengers. These include IP 3 and diacyl glycerol which activate internal receptors on the sarcoplasmic reticulum, which contain intracellular Ca 2+ stores (pharmacomechanical coupling) [25,26].…”

“…5-HT 2A receptors together with 5-HT 1B /5-HT 1D activation are primarily responsible for the contractile effects of 5-HT. The 5-HT 2A receptor is coupled to G q proteins and activates phospholipase C resulting in increased levels of the IP 3 inositol, while 5-HT 1B and 5-HT 1D receptors are coupled to adenyl cyclase, the G i/0 protein inhibitor [26,27].…”

Vascular Pathways of Testosterone: Clinical Implications

“…Concerning the effects on ion channels, several studies suggested that T exerts its vasodilatory effects by modulating different K + and/or Ca 2+ channels [15,21,[32][33][34]. The vascular tone is controlled by the ion flow, and the activation of K + channels represents the key mechanism involved in the relaxation [35,36]. This activation of K + channels causes a membrane hyperpolarization that closes the Ca 2+ channels, leading to vasorelaxation [37,38], and showing the close relationship between the channels mentioned.…”

Clinical Importance of the Human Umbilical Artery Potassium Channels

“…Moreover, the electrophysiological measurements using the patch-clamp technique showed that the amplitudes of the basal potassium currents in each channel are very different [ 1 , 5 ]. Currently, there are four different types of K + channels described in SMCs from the human umbilical artery: K V , K Ca , Kir, and 2-pore domain K + (K 2P ) channels ( Figure 1 ) [ 9 , 10 ]. However, the presence of intermediate-conductance Ca 2+ -activated K + channels (IK Ca ), one subtype of K Ca , has never been demonstrated [ 9 , 10 ].…”