Chronic intrauterine pulmonary hypertension decreases calcium-sensitive potassium channel mRNA expression

Chronic intrauterine pulmonary hypertension decreases calcium-sensitive potassium channel mRNA expression
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DOI:
10.1152/ajplung.2000.279.5.l857
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发表时间:
2000-11-01
影响因子:
4.9
通讯作者:
Abman, SH
Abman, SH
中科院分区:
医学2区
文献类型:
--
作者:
Cornfield, DN;Resnik, ER;Abman, SH

文献摘要

被引文献

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钙敏感性钾(K-Ca)通道在介导围产期肺血管舒张中起关键作用。由于新生儿持续性肺动脉高压(PPHN)的婴儿对出生相关刺激的血管舒张反应减弱,我们假设PPHN中肺K-Ca通道基因表达降低。为了验证这一假设,我们测量了K-Ca通道基因表达的远端肺匀浆从两个胎羊与严重的肺动脉高压所造成的长期压缩动脉导管和年龄匹配,假手术动物(对照组)。动脉导管压迫至少9天后,处死胎羊。为了确定肺K-Ca通道mRNA水平,针对K-Ca通道的已知序列设计引物,并用于半定量RT-PCR,以肺18 S rRNA含量作为内部对照。与对照组相比,PPHN组肺K-Ca通道mRNA含量降低26 ± 6%(P< 0.02),而肺电压门控K+ 2.1 mRNA含量无变化。我们的结论是,肺K-Ca通道mRNA的表达减少,在绵羊模型的PPHN。K-Ca通道基因表达降低可能是PPHN肺血管反应性异常的原因之一。
Calcium-sensitive potassium (K-Ca) channels play a critical role in mediating perinatal pulmonary vasodilation. Because infants with persistent pulmonary hypertension of the newborn (PPHN) have blunted vasodilator responses to birth-related stimuli, we hypothesized that lung K-Ca channel gene expression is decreased in PPHN. To test this hypothesis, we measured K-Ca channel gene expression in distal lung homogenates from both fetal lambs with severe pulmonary hypertension caused by prolonged compression of the ductus arteriosus and age-matched, sham-operated animals (controls). After at least 9 days of compression of the ductus arteriosus, fetal lambs were killed. To determine lung K-Ca channel mRNA levels, primers were designed against the known sequence of the K-Ca channel and used in semiquantitative RT-PCR, with lung 18S rRNA content as an internal control. Compared to that in control lambs, lung K-Ca channel mRNA content in the PPHN group was reduced by 26 +/- 6% (P< 0.02), whereas lung voltage-gated K+ 2.1 mRNA content was unchanged. We conclude that lung K-Ca channel mRNA expression is decreased in an ovine model of PPHN. Decreased K-Ca channel gene expression may contribute to the abnormal pulmonary vascular reactivity associated with PPHN.