Upregulation of endothelial cell Ca2+ signaling contributes to pregnancy-enhanced vasodilation of rat uteroplacental arteries
Upregulation of endothelial cell Ca2+ signaling contributes to pregnancy-enhanced vasodilation of rat uteroplacental arteries
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DOI：
10.1152/ajpheart.00813.2005
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发表时间：
2006-05-01
影响因子：
4.8
通讯作者：
Goecks, T
中科院分区：
文献类型：
--
作者：
Gokina, NI;Goecks, T
正常妊娠的特征是由于母体子宫血管系统的生长和重塑以及子宫动脉的血管舒张增强而导致子宫血流增加。本研究的目的是研究内皮细胞Ca 2+信号在增强内皮介导的血管舒张的子宫胎盘动脉在妊娠晚期的作用。我们进行了基于Fura-2的测量的细胞内Ca 2+浓度（[Ca 2 +]i）的内皮细胞的细胞质中的直径同时在加压子宫动脉从非妊娠（NP）和晚期妊娠（LP）大鼠。与NP对照组相比，LP大鼠动脉中内皮细胞[Ca 2 +]（i）的基础水平较高。细胞外Ca ~（2+）的减少导致LP大鼠动脉基础[Ca ~（2+）]（i）水平显著高于NP大鼠。Mn 2+诱导的Fura-2荧光猝灭率在妊娠晚期显著升高，这表明增加的Ca 2+内流是内皮细胞中[Ca 2 +]（i）基础水平增加的原因。腔内压力升高导致内皮细胞[Ca 2 +]（i）短暂增加，在妊娠晚期显著增强。与NP大鼠相比，LP大鼠动脉中ACh诱导的[Ca 2 +]（i）和血管舒张反应显著增强，BAPTA处理可消除[Ca 2 +]（i），表明[Ca 2 +]（i）升高在内皮源性血管舒张剂产生中的关键作用。总之，这些结果表明，晚期妊娠是一个国家的增强基础和刺激的Ca 2+信号在子宫血管内皮细胞，这可能是一个重要的基础机制，增强血管舒张在母体子宫循环。
Normal pregnancy is characterized by an increased uterine blood flow due to growth and remodeling of the maternal uterine vasculature and enhanced vasodilation of the uterine arteries. The objective of the present study was to examine the role of endothelial cell Ca2+ signaling in augmented endothelium-mediated vasodilation of uteroplacental arteries in late pregnancy. We performed fura-2-based measurements of the intracellular Ca2+ concentration ([Ca2+]i) in the cytoplasm of endothelial cells simultaneously with diameter in pressurized uterine arteries from nonpregnant (NP) and late-pregnant ( LP) rats. Basal levels of endothelial cell [Ca2+](i) were higher in arteries from LP rats compared with NP controls. Withdrawal of extracellular Ca2+ resulted in a decrease in the level of basal [Ca2+](i) that was significantly larger in arteries of LP than NP rats. The rate of Mn2+-induced quenching of fura-2 fluorescence was significantly elevated in late pregnancy, implicating augmented Ca2+ influx as a cause of increased basal levels of [Ca2+](i) in endothelial cells. Elevation of intraluminal pressure resulted in a transient increase in endothelial [Ca2+](i) that was markedly potentiated in late gestation. ACh-induced [Ca2+](i) and vasodilator responses were significantly augmented in arteries of LP compared with NP rats and were abolished by BAPTA treatment, demonstrating a critical role of [Ca2+](i) elevation in the production of endothelium-derived vasodilators. Together, these results indicate that late pregnancy is a state of enhanced basal and stimulated Ca2+ signaling in endothelial cells of uterine vessels, which may represent an important underlying mechanism for augmented vasodilation in the maternal uterine circulation.