Center for Preinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
Curr Vasc Pharmacol. 2013 Sep;11(5):737-47. doi: 10.2174/1570161111311050011.
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.
在正常妊娠过程中，子宫血管张力显著降低，导致子宫血流明显增加，这对胎儿发育和生长至关重要。妊娠期间慢性缺氧可能会对子宫血管张力的正常适应产生不利影响，并增加子痫前期和胎儿宫内生长受限的风险。在这篇综述中，我们提出了证据，表明 K+通道的调节是子宫血管张力适应妊娠和缺氧的重要机制。在动脉平滑肌细胞中已鉴定出四种类型的 K+通道：1）电压依赖性 K+（Kv）通道，2）Ca2+激活的 K+（KCa）通道，3）内向整流 K+（KIR）通道和 4）ATP 敏感性 K+（KATP）通道。妊娠通过下调蛋白激酶 C 信号转导在子宫和其他血管床中差异增强 K+通道的表达和活性，导致子宫血管张力降低和子宫血流增加。性激素在介导子宫血管中 K+通道的妊娠改变中起着重要作用。此外，慢性缺氧通过调节甾体激素/受体介导的信号转导改变子宫血管 K+通道的表达和活性，导致妊娠期间子宫血管张力增加。
