Hypoxic fetoplacental vasoconstriction in humans is mediated by potassium channel inhibition
Hypoxic fetoplacental vasoconstriction in humans is mediated by potassium channel inhibition
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DOI：
10.1152/ajpheart.01033.2001
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发表时间：
2002-12-01
影响因子：
4.8
通讯作者：
Archer, SL
中科院分区：
文献类型：
--
作者：
Hampl, V;Bíbová, J;Archer, SL
胎盘中胎儿与母体的血流匹配是最佳胎儿血氧合所必需的，可能通过缺氧性胎儿胎盘血管收缩（HFPV）发生。我们假设HFPV是由胎儿胎盘血管平滑肌中的K+通道抑制介导的，就像在其他几种O-2敏感组织中一样。使用以恒定流速灌注的离体人胎盘子叶，我们发现缺氧可逆地增加灌注压> 20%。HFPV不受环氧合酶或一氧化氮合酶抑制的影响。HFPV和电压依赖性K+（K-v）通道抑制剂4-氨基吡啶以非累加方式增加压力，表明它们通过共同机制起作用。伊比利亚毒素是一种大电导Ca ~（2+）敏感性K ~+（BKCa）通道抑制剂，对常氧压力影响不大。免疫印迹和RT-PCR显示，在外周胎儿胎盘血管的几个假定的O-2敏感的K+通道的表达。在膜片钳实验与平滑肌细胞分离的外周胎儿胎盘动脉，缺氧可逆地抑制K-V，但不BKCa或ATP依赖性电流。我们的结论是，人胎儿胎盘血管收缩缺氧反应。这种反应在很大程度上是由缺氧抑制小胎儿胎盘动脉平滑肌中的K-v通道介导的。
Fetal to maternal blood flow matching in the placenta, necessary for optimal fetal blood oxygenation, may occur via hypoxic fetoplacental vasoconstriction (HFPV). We hypothesized that HFPV is mediated by K+ channel inhibition in fetoplacental vascular smooth muscle, as occurs in several other O-2-sensitive tissues. With the use of an isolated human placental cotyledon perfused at a constant flow rate, we found that hypoxia reversibly increased perfusion pressure by >20%. HFPV was unaffected by cyclooxygenase or nitric oxide synthase inhibition. HFPV and 4-aminopyridine, an inhibitor of voltage-dependent K+ (K-v) channels, increased pressure in a nonadditive manner, suggesting they act via a common mechanism. Iberiotoxin, a large conductance Ca2+- sensitive K+ (BKCa) channel inhibitor, had little effect on normoxic pressure. Immunoblotting and RT-PCR showed expression of several putative O-2-sensitive K+ channels in peripheral fetoplacental vessels. In patch-clamp experiments with smooth muscle cells isolated from peripheral fetoplacental arteries, hypoxia reversibly inhibited K-v but not BKCa or ATP-dependent currents. We conclude that human fetoplacental vessels constrict in response to hypoxia. This response is largely mediated by hypoxic inhibition of K-v channels in the smooth muscle of small fetoplacental arteries.