High Altitude Reduces NO-Dependent Myometrial Artery Vasodilator Response During Pregnancy
High Altitude Reduces NO-Dependent Myometrial Artery Vasodilator Response During Pregnancy
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DOI：
10.1161/hypertensionaha.119.12641
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发表时间：
2019-06-01
期刊：
影响因子：
8.3
通讯作者：
Moore, Lorna G.
中科院分区：
文献类型：
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作者：
Lorca, Ramon A.;Lane, Sydney L.;Moore, Lorna G.
高海拔（HA）居住的慢性缺氧减少了妊娠期间的子宫动脉血流，可能导致先兆子痫和宫内生长受限的频率增加。我们假设，这种较少的妊娠血流量上升部分是由于子宫肌层动脉（MA）的血管舒张减少。在这里，我们评估了高海拔（2902 +/- 39 m）或低海拔（LA; 1669 +/- 10 m）健康居民的MA血管反应性。MA收缩反应氯化钾，苯肾上腺素，或血栓素A2激动剂U46619没有不同的LA和HA妇女。乙酰胆碱可使苯肾上腺素或U466119预收缩LA的MAs，但对HA MAs无影响。相比之下，另一种血管扩张剂，缓激肽，放松MA从两个高度相似。在LA，NO合成酶抑制剂L-N-G-硝基精氨酸甲酯降低乙酰胆碱和缓激肽血管舒张分别为56%和33%。L-N-G-硝基精氨酸甲酯加考克斯（环氧合酶）抑制剂吲哚美辛对乙酰胆碱和缓激肽血管舒张的作用（分别减少68%和42%）与去除内皮（分别减少78%和50%）相似，表明LA主要依赖NO的血管舒张。然而，在HA，L-N-G-硝基精氨酸甲酯并没有改变缓激肽血管舒张，而吲哚美辛或内皮细胞去除减少了28%和72%，分别表明在HA受损的NO信号。表明损伤是eNOS（内皮NO合成酶）的下游，HA减弱了NO供体硝普钠引起的血管舒张。我们的结论是，减少NO依赖性MA血管舒张可能有助于减少子宫胎盘灌注HA妊娠。
The chronic hypoxia of high-altitude (HA) residence reduces uterine artery blood flow during pregnancy, likely contributing to an increased frequency of preeclampsia and intrauterine growth restriction. We hypothesized that this lesser pregnancy blood flow rise was due, in part, to reduced vasodilation of myometrial arteries (MAs). Here, we assessed MA vasoreactivity in healthy residents of high (2902 +/- 39 m) or low altitude (LA; 1669 +/- 10 m). MA contractile responses to potassium chloride, phenylephrine, or the thromboxane A2 agonist U46619 did not differ between LA and HA women. Acetylcholine vasodilated phenylephrine or U466119 preconstricted MAs at LA, yet had no effect on HA MAs. In contrast, another vasodilator, bradykinin, relaxed MAs from both altitudes similarly. At LA, the NO synthase inhibitor L-N-G-nitroarginine methyl ester decreased both acetylcholine and bradykinin vasodilation by 56% and 33%, respectively. L-N-G-nitroarginine methyl ester plus the COX (cyclooxygenase) inhibitor indomethacin had similar effects on acetylcholine and bradykinin vasodilation (68% and 42% reduction, respectively) as did removing the endothelium (78% and 50% decrease, respectively), suggesting a predominantly NO-dependent vasodilation at LA. However, at HA, L-N-G-nitroarginine methyl ester did not change bradykinin vasodilation, whereas indomethacin or endothelium removal decreased it by 28% and 72%, respectively, indicating impaired NO signaling at HA. Suggesting that the impairment was downstream of eNOS (endothelial NO synthase), HA attenuated the vasodilation elicited by the NO donor sodium nitroprusside. We concluded that reduced NO-dependent MA vasodilation likely contributes to diminished uteroplacental perfusion in HA pregnancies.