From the Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Science, University of British Columbia, Kelowna, Canada (M.M.T., P.N.A.).
Neurovascular Health Lab, Faculty of Kinesiology, Sport and Recreation, University of Alberta, Edmonton, Canada (M.M.T.).
Circ Res. 2020 Jul 3;127(2):e1-e13. doi: 10.1161/CIRCRESAHA.119.316053. Epub 2020 Apr 9.
Chronic 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.
To 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.
We 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%, all ≤0.02); and in Andeans with EE compared with non-EE (changes in forearm vascular conductance at ACh3: -36.4%, =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 (=0.012), but this effect was not observed in the EE Andeans.
These 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.
慢性低氧暴露与低海拔地区交感神经活性升高和血管功能降低有关，安第斯高地居民因红细胞增多症（EE）而遭受过度的红细胞生成；然而，慢性交感神经活性升高与低氧诱导的血管功能障碍之间的机制联系尚未确定。
确定在高原环境下，交感神经活性升高对低海拔居民和有/无 EE 的安第斯高地居民的阻力动脉内皮依赖性舒张（EDD）和非内皮依赖性舒张的影响。
我们在海平面（344 米）下测试了 9 名健康的低海拔居民，随后在高海拔（4300 米）下进行了 14 至 21 天的实验，还在高海拔环境下测试了 6 名有 EE 的和 9 名无 EE 的永久性安第斯高地居民。使用乙酰胆碱（EDD）和硝普钠（非内皮依赖性舒张）的动脉内输注（3 个渐进剂量）来评估血管功能，然后在局部α+β肾上腺素能受体阻断（酚妥拉明和普萘洛尔）前后进行。在休息和药物输注期间记录了动脉内血压、心率以及同时的肱动脉直径和血流速度。计算了前臂血管传导能力的变化。主要发现如下：（1）慢性缺氧降低了低海拔居民的 EDD（从海平面开始的前臂血管传导能力变化：ACh1：-52.7±19.6%，ACh2：-25.4±38.7%，ACh3：-35.1±34.7%，均≤0.02）；并且在有 EE 的安第斯居民中比在无 EE 的安第斯居民中降低（ACh3 时的前臂血管传导能力变化：-36.4%，=0.007）。高海拔地区的低海拔居民的肾上腺素能阻断完全恢复了 EDD，并且在 EE 和非 EE 安第斯居民之间使 EDD 正常化。（2）慢性缺氧对低海拔居民的非内皮依赖性舒张没有影响，并且在 EE 和非 EE 安第斯居民之间也没有差异；然而，非 EE 安第斯居民的 EID 在肾上腺素能阻断后增加（=0.012），但在 EE 安第斯居民中没有观察到这种效果。
这些数据表明，慢性缺氧通过低海拔地区和 EE 安第斯居民中的α-肾上腺素能信号降低来降低 EDD。这些血管机制对于理解急性和慢性高原适应的生理后果具有重要意义。
