Effect of long-term high-altitude hypoxia on fetal pulmonary vascular contractility.
Effect of long-term high-altitude hypoxia on fetal pulmonary vascular contractility.
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DOI：
10.1152/japplphysiol.01314.2007
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发表时间：
2008-04
影响因子：
3.3
通讯作者：
Qin Xue;C. Ducsay;L. Longo;Lubo Zhang
中科院分区：
文献类型：
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作者：
Qin Xue;C. Ducsay;L. Longo;Lubo Zhang
胎儿和/或新生儿缺氧与肺动脉高压风险增加相关。本研究验证了长期高原低氧血症通过内皮型一氧化氮合酶（eNOS）差异介导的差异调节胎儿肺动脉（PA）和肺静脉（PV）收缩性的假设。从在海平面（300 m）或3，801 m高海拔（动脉Po（2）为60 Torr）下保持110天的妊娠母羊的近足月胎儿中分离PA和PV。缺氧对肺血管中壁厚度没有影响，也没有改变KCl诱导的收缩。在PA中，缺氧显著增加去甲肾上腺素（NE）引起的收缩，eNOS抑制剂N（G）-硝基-L-精氨酸（l-NNA）不影响这种收缩。在PV中，缺氧对NE诱导的收缩没有影响。L-NNA显著增加NE诱导的对照和缺氧PV收缩。在l-NNA的存在下，NE引起的收缩PV在缺氧羔羊与常氧动物相比显着减少。乙酰胆碱引起肺静脉舒张，但不引起肺动脉舒张，低氧使肺静脉pD（2）和乙酰胆碱舒张的最大反应显著降低。此外，缺氧显着降低硝普钠诱导的PA和PV舒张的最大反应。常氧组绵羊肺动脉和肺静脉内皮细胞中均检测到eNOS，肺静脉中eNOS蛋白表达水平显著高于肺动脉。缺氧对PA或PV中的eNOS水平没有显着影响。结果表明，胎儿肺动脉和静脉的异质性，在长期高原缺氧，并建议一个可能的共同机制下游的NO在胎儿肺血管反应，在子宫内慢性缺氧。
Hypoxia in the fetus and/or newborn is associated with an increased risk of pulmonary hypertension. The present study tested the hypothesis that long-term high-altitude hypoxemia differentially regulates contractility of fetal pulmonary arteries (PA) and veins (PV) mediated by differences in endothelial NO synthase (eNOS). PA and PV were isolated from near-term fetuses of pregnant ewes maintained at sea level (300 m) or high altitude of 3,801 m for 110 days (arterial Po(2) of 60 Torr). Hypoxia had no effect on the medial wall thickness of pulmonary vessels and did not alter KCl-induced contractions. In PA, hypoxia significantly increased norepinephrine (NE)-induced contractions, which were not affected by eNOS inhibitor N(G)-nitro-l-arginine (l-NNA). In PV, hypoxia had no effect on NE-induced contractions in the absence of l-NNA. l-NNA significantly increased NE-induced contractions in both control and hypoxic PV. In the presence of l-NNA, NE-induced contractions of PV were significantly decreased in hypoxic lambs compared with normoxic animals. Acetylcholine caused relaxations of PV but not PA, and hypoxia significantly decreased both pD(2) and the maximal response of acetylcholine-induced relaxation in PV. Additionally, hypoxia significantly decreased the maximal response of sodium nitroprusside-induced relaxations of both PA and PV. eNOS was detected in the endothelium of both PA and PV, and eNOS protein levels were significantly higher in PV than in PA in normoxic lambs. Hypoxia had no significant effect on eNOS levels in either PA or PV. The results demonstrate heterogeneity of fetal pulmonary arteries and veins in response to long-term high-altitude hypoxia and suggest a likely common mechanism downstream of NO in fetal pulmonary vessel response to chronic hypoxia in utero.