Chronic hypoxia inhibits contraction of fetal arteries by increased endothelium-derived nitric oxide and prostaglandin synthesis.
Chronic hypoxia inhibits contraction of fetal arteries by increased endothelium-derived nitric oxide and prostaglandin synthesis.
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慢性缺氧通过增加内皮源性一氧化氮和前列腺素合成来抑制胎儿动脉收缩。
DOI：
10.1016/j.jsgi.2004.05.008
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Zhou,Hui
中科院分区：
文献类型：
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作者：
Thompson,LorenP;Aguan,Kripamoy;Zhou,Hui
目的：慢性低氧引起胎儿心输出量的重新分配，其机制尚不清楚。我们验证了慢性低氧改变近期胎鼠动脉血管反应性的假设。方法：妊娠豚鼠(50天，足月=65天)暴露于常氧(室内空气)和低氧(12%O2)14天。将麻醉胎儿的颈动脉环安装在肌图仪上进行测力。分别在INDO(INDO，10-5M)和INDO加L精氨酸(LNA，10-4M)或INDO加N6-亚氨基乙基-L赖氨酸(LNIL，5×10-5M，选择性诱导型一氧化氮合酶抑制剂)存在和不存在INDO(INDO，10-5M)和INDO+N6-亚氨基乙基-L赖氨酸(LNIL，5×10-5M，选择性诱导型一氧化氮合酶抑制剂)存在和不存在INDO(INDO，10-5M)和INDO+N6-亚氨基乙基-L赖氨酸(LNIL，5×10-5M，选择性诱导型一氧化氮合酶抑制剂)的情况下，测量对累积添加前列腺素F2α(PGF2α，10-9M到10-5M)、U46619(血栓素类似物10-12M到12-6M)和KCl10到120 mM的收缩反应。用14C-L-精氨酸转化为14C-L-瓜氨酸的方法测定离体动脉中一氧化氮合酶的活性。结果：在对照条件下，缺氧降低了对前列腺素F_2α和U46619的收缩反应。与常氧对照组相比，INDO单独和INDO+LNA后低氧动脉对两种激动剂的最大收缩增加。内皮剥离消除了两组之间的差异。缺氧对KCL收缩无明显影响。LNIL可增强PGF_2α的最大收缩，但组间无明显差异。低氧可使(P<；.05)总一氧化氮合酶活性和钙依赖的一氧化氮合酶活性分别增加1.7倍和2.1倍，但对钙非依赖性的活性无影响。结论：慢性低氧通过增加血管扩张剂前列腺素和一氧化氮的贡献来改变胎儿颈动脉的血管反应性，提示慢性低氧可能改变局部血管机制。
Objective:Chronic hypoxia causes redistribution of fetal cardiac output by mechanisms poorly understood. We tested the hypothesis that chronic hypoxia alters vascular reactivity of arteries from near-term fetal guinea pigs.Methods:Pregnant guinea pigs (50 days, term = 65 days) were exposed to either normoxia (room air) or hypoxia (12% O2) for 14 days. Carotid artery ring segments from anesthetized fetuses were mounted onto myographs for measurement of force. Contractile responses to cumulative addition of prostaglandin F2α(PGF2α, 10-9M to 10-5M), U46619, a thromboxane mimetic (10-12M to 12-6M), and KCl (10 to 120 mM) were measured in the presence and absence of INDO (INDO, 10-5M) alone and INDO plus mintro-L-arginine (LNA, 10-4M), or INDO plus N6-iminoethyl-L-lysine (LNIL, 5 × 10-5M, a selective iNOS inhibitor), and measured in endothelium-intact and denuded arteries. Nitric oxide synthase (NOS) activity was measured in isolated arteries by14C-L-arginine to14C-L-citrulline conversion.Results:Hypoxia decreased contractile responses to both PGF2αand U46619 under control conditions. Maximal contraction to both agonists was increased in hypoxemic arteries after INDO alone and INDO + LNA compared to normoxic controls. Endothelium-denudation abolished the differences between the groups. KCl contration was unaffected by hypoxia. LNIL potentiated maximal PGF2αcontraction but was similar between groups. Hypoxia increased (P < .05) total and Ca2+-dependent NOS activities by 1.7- and 2.1-fold, respectively, but had no effect on Ca2+-independent activity.Conclusion:Chronic hypoxia alters vascular reactivity of fetal carotid arteries by increasing the contribution of both vasodilator prostaglandins and nitric oxide and suggests that changes in local vascular mechanisms may be altered by chronic hypoxia.