Chronic hypoxia-mediated oxidative stress downregulates the large-conductance Ca2+-activated K+ channel activity in uterine arteries in pregnancy (889.4)

Chronic hypoxia during pregnancy constitutes a major insult to maternal cardiovascular homeostasis, leading to complicated uteroplacental circulation. We recently demonstrated that long term high‐altitude hypoxia enhanced uterine arterial myogenic tone, which was mediated by the downregulation of the large‐conductance Ca 2+ ‐activated K + channel (BK Ca ) activity via enhanced oxidative stress. In the present study we tested the hypothesis that chronic hypoxia exposure directly increases generation of reactive oxygen species (ROS) in the uterine artery from pregnant sheep, which in turn suppresses BK Ca channel activity in VSMCs of the vessel. Uterine arteries were isolated from near‐term (~140 days) pregnant sheep and incubated under 21% or 10.5% O 2 for 48 hours at 37 °C. Exposure to chronic hypoxia significantly increased ROS levels and depressed the BK Ca current density ( p < 0.05). Neither ROS levels nor BK Ca current density in tissues cultured in 21% O 2 were altered by the antioxidant N‐acetylcysteine (NAC). However, the increased ROS level and depressed BK Ca current density during exposure to chronic hypoxia were ablated by NAC. Our findings suggest a direct effect of chronic hypoxia in suppressing the function of BK Ca channels in uterine arteries through increased generation of ROS, which may contribute to the increased myogenic tone of uterine arteries in response to chronic hypoxia during gestation. Grant Funding Source : HL089012, HL110125