Chronic intrauterine pulmonary hypertension increases capacitative calcium entry in fetal pulmonary artery smooth muscle cells.
Chronic intrauterine pulmonary hypertension increases capacitative calcium entry in fetal pulmonary artery smooth muscle cells.
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DOI：
10.1152/ajplung.00327.2006
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发表时间：
2007-04
期刊：
影响因子：
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通讯作者：
E. Resnik;M. Keck;David Sukovich;J. Herron;D. Cornfield
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文献类型：
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作者：
E. Resnik;M. Keck;David Sukovich;J. Herron;D. Cornfield
氧气导致围产期肺扩张。虽然胎儿肺动脉平滑肌细胞（PA SMC）通常对氧（O2）张力的急性增加有反应，细胞内[Ca（2+）] i（[Ca（2+）]i）降低，但O2张力的急性增加对来自慢性宫内肺动脉高压（PHTN）羔羊的PA SMC的[Ca（2+）] i没有净效应。本实验系列测试的假设，急性增加O2张力降低正常，但不高血压，胎儿PA SMC的容量性钙离子内流（CCE）。在妊娠127天结扎动脉导管（PHTN）或假手术（对照）后，从妊娠晚期胎羊中分离PA SMC。从远端PA（>或=第4代）分离PA SMC，并在原代培养物中在缺氧条件（约25 Torr）下维持。Fura 2负载后，PA SMC中的表观[Ca 2 +]i被确定为340-与380-nm荧光强度的比率。在缺氧和常氧条件下，环匹阿尼酸（CPA）增加[Ca 2 +]i在PHTN比对照PA SMC。CCE测定在PA SMC缺氧和常氧条件下，灌流后与零细胞外Ca 2+和细胞内存储耗尽与CPA，然后灌流与含Ca 2+的溶液，在电压操作的钙通道阻滞剂的存在下。在急性和持续常氧条件下，与对照PA SMC相比，PHTN中的CCE增加。对照组瞬时受体电位通道基因表达高于PHTN PA SMC。PHTN可能部分通过调节PA SMC CCE而损害围产期肺血管舒张。
Oxygen causes perinatal pulmonary dilatation. Although fetal pulmonary artery smooth muscle cells (PA SMC) normally respond to an acute increase in oxygen (O2) tension with a decrease in cytosolic calcium ([Ca2+]i), an acute increase in O2 tension has no net effect on [Ca(2+)](i) in PA SMC derived from lambs with chronic intrauterine pulmonary hypertension (PHTN). The present experimental series tests the hypothesis that an acute increase in O2 tension decreases capacitative calcium entry (CCE) in normal, but not hypertensive, fetal PA SMC. PA SMC were isolated from late-gestation fetal lambs after either ligation of the ductus arteriosus (PHTN) or sham (control) operation at 127 days gestation. PA SMC were isolated from the distal PA (>or=4th generation) and maintained under hypoxic conditions ( approximately 25 Torr) in primary culture. After fura 2 loading, apparent [Ca2+]i in PA SMC was determined as the ratio of 340- to 380-nm fluorescence intensity. Under both hypoxic and normoxic conditions, cyclopiazonic acid (CPA) increased [Ca2+]i more in PHTN than in control PA SMC. CCE was determined in PA SMC under hypoxic and normoxic conditions, after superfusion with zero extracellular Ca2+ and intracellular store depletion with CPA, followed by superfusion with Ca2+-containing solution, in the presence of the voltage-operated calcium channel blockade. CCE was increased in PHTN compared with control PA SMC under conditions of both acute and sustained normoxia. Transient receptor potential channel gene expression was greater in control compared with PHTN PA SMC. PHTN may compromise perinatal pulmonary vasodilation, in part, by modulating PA SMC CCE.