From the Division of Reproductive Sciences (R.A.L., S.L.L., E.S.B., L.G.M.), University of Colorado Denver, Aurora.
BA/BS-MD Program, College of Liberal Arts and Sciences (H.N., H.Y.), University of Colorado Denver, Aurora.
Hypertension. 2019 Jun;73(6):1319-1326. doi: 10.1161/HYPERTENSIONAHA.119.12641.
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-nitroarginine methyl ester decreased both acetylcholine and bradykinin vasodilation by 56% and 33%, respectively. L-N-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-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.
高海拔（HA）居住的慢性缺氧会减少怀孕期间子宫动脉的血流量，这可能导致子痫前期和宫内生长受限的发生率增加。我们假设，这种妊娠血流量增加减少的部分原因是子宫肌层动脉（MAs）的舒张减少。在这里，我们评估了健康的高海拔（2902±39 m）和低海拔（LA；1669±10 m）居民的 MA 血管反应性。LA 和 HA 女性的钾氯、苯肾上腺素或血栓素 A2 激动剂 U46619 对 MA 的收缩反应没有差异。乙酰胆碱舒张苯肾上腺素或 U466119 预收缩的 MA 在 LA，但对 HA MA 没有作用。相比之下，另一种血管扩张剂缓激肽同样放松了来自两个海拔高度的 MA。在 LA，一氧化氮合酶抑制剂 L-N-硝基精氨酸甲酯使乙酰胆碱和缓激肽舒张分别减少了 56%和 33%。L-N-硝基精氨酸甲酯加环氧化酶（COX）抑制剂吲哚美辛对乙酰胆碱和缓激肽舒张的作用相似（分别减少 68%和 42%），去除内皮（分别减少 78%和 50%）也是如此，这表明在 LA 主要是一氧化氮依赖性血管舒张。然而，在 HA，L-N-硝基精氨酸甲酯没有改变缓激肽的血管舒张，而吲哚美辛或内皮去除分别减少了 28%和 72%，这表明在 HA 中一氧化氮信号受损。表明损伤发生在 eNOS（内皮型一氧化氮合酶）下游，HA 减弱了一氧化氮供体硝普钠引起的血管舒张。我们得出结论，NO 依赖性 MA 血管舒张减少可能导致 HA 妊娠中胎盘灌注减少。
