Abstract
Chorionic plate arteries (CPA) are located at the maternofetal interface where they are able to respond to local metabolic changes. Unlike many other types of vasculature, the placenta lacks nervous control and requires autoregulation for controlling blood flow. The placental circulation, which is of low-resistance, may become hypoxic easily leading to fetal acidosis and fetal distress however the role of the ion channels in these circumstances is not well-understood. Active potassium channel conductances that are subject to local physicochemical modulation may serve as pathways through which such signals are transduced. The aim of this study was to investigate the modulation of CPA by pH and the channels implicated in these responses using wire myography. CPA were isolated from healthy placentae and pre-contracted with U46619 before testing the effects of extracellular pH using 1 M lactic acid over the pH range 7.4 - 6.4 in the presence of a variety of ion channel modulators. A change from pH 7.4 to 7.2 produced a 29±3% (n = 9) relaxation of CPA which increased to 61±4% at the lowest pH of 6.4. In vessels isolated from placentae of women with pre-eclampsia (n = 6), pH responses were attenuated. L-methionine increased the relaxation to 67±7% (n = 6; p<0.001) at pH 6.4. Similarly the TASK 1/3 blocker zinc chloride (1 mM) gave a maximum relaxation of 72±5% (n = 8; p<0.01) which compared with the relaxation produced by the TREK-1 opener riluzole (75±5%; n = 6). Several other modulators induced no significant changes in vascular responses. Our study confirmed expression of several ion channel subtypes in CPA with our results indicating that extracellular pH within the physiological range has an important role in controlling vasodilatation in the human term placenta.
Highlights
Throughout pregnancy, it is essential for the placenta to manage acid-base balance within a narrow pH range in order to minimise adverse effects on fetal growth and development
The effects of voltage-gated, calcium-sensitive and K2P channel modulators were investigated by direct application to resistance-sized chorionic plate arteries (CPA) preconstricted with U46619
Levels of metabolic acids such as lactic acid have been shown to increase when tissue perfusion is low as may occur during certain pregnancy disorders or during uterine contractions accompanying normal labour [28, 29]
Summary
Throughout pregnancy, it is essential for the placenta to manage acid-base balance within a narrow pH range in order to minimise adverse effects on fetal growth and development This is accomplished by eliminating acids formed by normal fetal and placental metabolism via the maternal circulation and through buffering provided principally by hemoglobin and bicarbonate [1, 2]. During labor, uterine contractions can occlude blood flow placental perfusion by compression of the uterine artery [3] This can lead to fetal hypoxia and acidosis monitoring of umbilical cord blood pH is a useful measure of fetal wellbeing, indicating the need for clinical intervention when pH poses a danger to fetal health [2]. Fetoplacental arteries are much less sensitive to vasoactive molecules that have potent effects in other vascular beds [4, 5] the effects of molecules and factors produced locally that have the capacity to alter placental vascular function have not been widely studied yet may highlight mechanisms by which control of fetoplacental vascular tone is achieved
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
