Abstract
During a normal course of pregnancy, uterine vascular tone is significantly decreased resulting in a striking increase in uterine blood flow, which is essential for fetal development and fetal growth. Chronic hypoxia during gestation may adversely affect the normal adaptation of uterine vascular tone and increase the risk of preeclampsia and fetal intrauterine growth restriction. In this review, we present evidence that the regulation of K+ channels is an important mechanism in the adaptation of uterine vascular tone to pregnancy and hypoxia. There are four types of K+ channels identified in arterial smooth muscle cells: 1) voltage-dependent K(+) (Kv) channels, 2) Ca2+-activated K(+) (KCa) channels, 3) inward rectifier K(+) (KIR) channels, and 4) ATP-sensitive K(+) (KATP) channels. Pregnancy differentially augments the expression and activity of K(+) channels via downregulation of protein kinase C signaling in uterine and other vascular beds, leading to decreased uterine vascular tone and increased uterine blood flow. Sex steroid hormones play an important role in the pregnancy- mediated alteration of K+ channels in the uterine vasculature. In addition, chronic hypoxia alters uterine vascular K(+) channels expression and activities via modulation of steroid hormones/receptors-mediated signaling, resulting in increased uterine vascular tone during pregnancy.