High altitude differentially modulates potassium channel-evoked vasodilation in pregnant human myometrial arteries

High-altitude (>2500 m or 8200 ft) residence reduces uterine artery blood flow during pregnancy, contributing to an increased incidence of preeclampsia and intrauterine growth restriction. However, not all pregnancies are affected by the chronic hypoxic conditions of high-altitude residence. K + channels play important roles in the uterine vascular adaptation to pregnancy, promoting a reduction in myogenic tone and an increase in blood flow. We hypothesized that, in pregnancies with normal fetal growth at high altitude, K + channel-dependent vasodilation of myometrial arteries is increased compared to those from healthy pregnant women at a lower altitude (~1700 m). Using pharmacological modulation of two K + channels, ATP-sensitive (K ATP ) and large-conductance Ca 2+ -activated (BK Ca ) K + channels, we assessed the vasodilation of myometrial arteries from AGA pregnancies in women living at high or low altitudes. In addition, we evaluated the localization of these channels in the myometrial arteries using immunofluorescence. Our results showed an endothelium-dependent increase in K ATP -dependent vasodilation in myometrial arteries from high vs. low altitude, whereas vasodilation induced by BK Ca activation was reduced in these vessels. Additionally, K ATP channel co-localization with endothelial markers was reduced in the high-altitude myometrial arteries, which suggested that the functional increase in K ATP activity may be by mechanisms other than regulation of channel localization. These observations highlight an important contribution of K + channels to the human uterine vascular adaptation to pregnancy at high altitude serving to maintain normal fetal growth under conditions of chronic hypoxia. We assessed the role of BK Ca and K ATP channels in the vasodilation of myometrial arteries from healthy pregnant women residing at low (2500 m). High-altitude residence increased the sensitivity of K ATP channels to the blocker glibenclamide in an endothelium dependent manner. Conversely, the sensitivity of the BK Ca channel blocker TEA was reduced in myometrial arteries from high-altitude women in a smooth muscle-dependent manner. Our findings highlight a possible mechanism of maternal vascular adaptation to pregnancy under conditions of chronic hypoxia to maintain a healthy pregnancy.