Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension
Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension
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DOI：
10.1152/ajplung.1997.272.5.l1005
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发表时间：
1997-05-01
影响因子：
4.9
通讯作者：
Morin, FC
中科院分区：
文献类型：
--
作者：
Shaul, PW;Yuhanna, IS;Morin, FC
一氧化氮（NO）由内皮(e) NO合成酶（NOS）产生，在胎儿到新生儿生命的心肺过渡中起关键作用。我们之前的研究表明，产前动脉导管结扎造成的肺动脉高压（PHT）胎儿羔羊的肺内动脉中no依赖性松弛减弱。在本研究中，我们确定了这是否由于肺eNOS表达的改变。在近期对照羔羊和10天前进行导管结扎的PHT羔羊的肺中评估eNOS和神经元NOS （nNOS）蛋白表达。PHT组eNOS蛋白表达降低49%。相比之下，nNOS蛋白丰度没有变化。与对照组相比，PHT组NOS酶活性也降低（60+/-3 vs 110+/-7 fmol）。Mg蛋白-1。分钟(1),分别)。在PHT肺中，eNOS mRNA丰度下降64%，与eNOS蛋白和NOS酶活性下降相似。因此，在羔羊胎儿PHT模型中，肺eNOS基因表达减弱。由于NO调节血管舒张和血管平滑肌生长，eNOS表达减少可能导致胎儿PHT血管反应性异常和肺循环过度肌肉化。
Nitric oxide (NO), produced by endothelial (e) NO synthase (NOS), is critically involved in the cardiopulmonary transition from fetal to neonatal life. We have previously shown that NO-dependent relaxation is attenuated in intrapulmonary arteries from fetal lambs with pulmonary hypertension (PHT) created by prenatal ligation of the ductus arteriosus. In the present study, we determined whether this is due to altered pulmonary eNOS expression. eNOS and neuronal NOS (nNOS) protein expression were assessed in lungs from near-term control lambs and PHT lambs that underwent ductal ligation 10 days earlier. eNOS protein expression was decreased 49% in PHT lung. In contrast, nNOS protein abundance was unchanged. NOS enzymatic activity was also diminished in PHT vs. control lung (60+/-3 vs. 110+/-7 fmol . mg protein-1 . min(-1), respectively). Paralleling the declines in eNOS protein and NOS enzymatic activity, eNOS mRNA abundance was decreased 64% in PHT lung. Thus pulmonary eNOS gene expression is attenuated in the lamb model of fetal PHT. Because NO modulates both vasodilation and vascular smooth muscle growth, diminished eNOS expression may contribute to both the abnormal vasoreactivity and the excessive muscularization of the pulmonary circulation in fetal PHT.