分子组织学与医学生理学杂志

Altitude-Induced Differential Effects on Potassium Channel-Mediated Vasodilation in Pregnant Human Myometrial Arteries

Abstract

Anna Lorca

Residing at high altitudes (>2500 m or 8200 ft) leads to a decline in blood flow through the uterine artery during pregnancy, contributing to a higher occurrence of preeclampsia and intrauterine growth restriction. Nevertheless, not all pregnancies experience the effects of prolonged hypoxia associated with high-altitude living. Potassium (K⁺) channels play a pivotal role in the uterine blood vessel adjustments during pregnancy, promoting the relaxation of muscle tone and an augmentation in blood circulation. We postulated that in pregnancies with normal fetal growth at high altitudes, there is an augmented K⁺ channel-mediated vasodilation in myometrial arteries compared to those in healthy pregnant women residing at lower altitudes (approximately 1700 m). Through the manipulation of two K⁺ channels the ATP-sensitive (KATP) and large-conductance Ca²⁺-activated (BKCa) K⁺ channels we evaluated the vasodilation response in myometrial arteries derived from pregnancies with appropriate gestational age (AGA) in women living at varying altitudes. Additionally, we investigated the spatial distribution of these channels within myometrial arteries using immunofluorescence techniques. Our findings revealed an increase in endothelium-dependent KATP-mediated vasodilation in myometrial arteries from high-altitude residents compared to those from lower altitudes, whereas vasodilation triggered by activation of BKCa channels was diminished in these arteries. Furthermore, the co-localization of KATP channels with endothelial markers was reduced in myometrial arteries from high-altitude residents, suggesting that the heightened KATP activity might be governed by mechanisms unrelated to channel localization regulation. These observations underscore the significant contribution of K⁺ channels to the adaptive response of human uterine blood vessels during pregnancy at high altitudes, crucial for maintaining normal fetal growth in the face of chronic hypoxia conditions.