The effect of pH and ion channel modulators on human placental arteries

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.