Global Reach 2018 Heightened α-Adrenergic Signaling Impairs Endothelial Function During Chronic Exposure to Hypobaric Hypoxia.
Global Reach 2018 Heightened α-Adrenergic Signaling Impairs Endothelial Function During Chronic Exposure to Hypobaric Hypoxia.
复制标题
Global Reach 2018 增强的α-肾上腺素信号传导会在慢性暴露于低压缺氧期间损害内皮功能。
DOI：
10.1161/circresaha.119.316053
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发表时间：
2020
影响因子：
20.1
通讯作者：
HearonJr,Christo
中科院分区：
文献类型：
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作者：
Tymko,MichaelM;Lawley,JustinS;Ainslie,PhilipN;Hansen,AlexanderB;Hofstaetter,Florian;Rainer,Simon;Amin,Sachin;Moralez,Gilbert;Gasho,Christopher;Vizcardo-Galindo,Gustavo;Bermudez,Daniela;Villafuerte,FranciscoC;HearonJr,Christo
基本原理长期缺氧与低地人和患有红细胞增多症（EE）的安第斯高地人的交感神经活动升高和血管功能降低有关；然而，长期升高的交感神经活动与缺氧引起的血管功能障碍之间的机制联系尚未确定。 目的 确定交感神经活动增强对有或没有 EE 的低地人和安第斯高地人的阻力动脉内皮依赖性扩张 (EDD) 和内皮非依赖性扩张的影响。方法和结果我们在海平面 (344 m) 和以下位置测试了健康的低地人 (n=9)高海拔（4300 m）14至21天，以及在高海拔有（n = 6）和没有（n = 9）EE的永久安第斯高地人。在局部α+β肾上腺素能受体阻断（酚妥拉明和普萘洛尔）之前和之后，使用动脉内输注（3个渐进剂量）乙酰胆碱（ACh；EDD）和硝普钠（内皮依赖性扩张）来评估血管功能。记录静息时和药物输注期间的动脉内血压、心率以及同时的肱动脉直径和血流速度。计算前臂血管电导的变化。主要发现是（1）慢性缺氧降低了低地人的EDD（前臂血管电导率相对于海平面的变化：ACh1：-52.7±19.6％，ACh2：-25.4±38.7％，ACh3：-35.1±34.7％，全部P≤0.02）；在安第斯山脉中，EE 与非 EE 相比（ACh3 处前臂血管电导的变化：-36.4%，P=0.007）。肾上腺素能封锁完全恢复了高海拔低地人的 EDD，并使 EE 和非 EE 安第斯人之间的 EDD 正常化。 (2) 慢性缺氧对低地人的内皮依赖性扩张没有影响，EE 和非 EE 安第斯人之间也没有检测到差异；然而，在非EE安第斯人中，肾上腺素能阻断后，EID增加（P=0.012），但在EE安第斯人中没有观察到这种效应。结论这些数据表明，在低地人和有EE的安第斯人中，慢性缺氧通过增强的α-肾上腺素信号传导来减少EDD。这些血管机制对于理解急性和慢性高海拔适应的生理后果具有重要意义。
RationaleChronic exposure to hypoxia is associated with elevated sympathetic nervous activity and reduced vascular function in lowlanders, and Andean highlanders suffering from excessive erythrocytosis (EE); however, the mechanistic link between chronically elevated sympathetic nervous activity and hypoxia-induced vascular dysfunction has not been determined.ObjectiveTo determine the impact of heightened sympathetic nervous activity on resistance artery endothelial-dependent dilation (EDD), and endothelial-independent dilation, in lowlanders and Andean highlanders with and without EE.Methods and ResultsWe tested healthy lowlanders (n=9) at sea level (344 m) and following 14 to 21 days at high altitude (4300 m), and permanent Andean highlanders with (n=6) and without (n=9) EE at high altitude. Vascular function was assessed using intraarterial infusions (3 progressive doses) of acetylcholine (ACh; EDD) and sodium nitroprusside (endothelial-independent dilation) before and after local α+β adrenergic receptor blockade (phentolamine and propranolol). Intraarterial blood pressure, heart rate, and simultaneous brachial artery diameter and blood velocity were recorded at rest and during drug infusion. Changes in forearm vascular conductance were calculated. The main findings were (1) chronic hypoxia reduced EDD in lowlanders (changes in forearm vascular conductance from sea level: ACh1: −52.7±19.6%, ACh2: −25.4±38.7%, ACh3: −35.1±34.7%, allP≤0.02); and in Andeans with EE compared with non-EE (changes in forearm vascular conductance at ACh3: −36.4%,P=0.007). Adrenergic blockade fully restored EDD in lowlanders at high altitude, and normalized EDD between EE and non-EE Andeans. (2) Chronic hypoxia had no effect on endothelial-independent dilation in lowlanders, and no differences were detected between EE and non-EE Andeans; however, EID was increased in the non-EE Andeans after adrenergic blockade (P=0.012), but this effect was not observed in the EE Andeans.ConclusionsThese data indicate that chronic hypoxia reduces EDD via heightened α-adrenergic signaling in lowlanders and in Andeans with EE. These vascular mechanisms have important implications for understanding the physiological consequences of acute and chronic high altitude adaptation.