Department of Biology, McMaster University, Hamilton, Ontario, Canada.
Division of Respirology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Am J Physiol Regul Integr Comp Physiol. 2021 Jun 1;320(6):R800-R811. doi: 10.1152/ajpregu.00282.2020. Epub 2021 Apr 7.
Hypoxia at high altitude can constrain metabolism and performance and can elicit physiological adjustments that are deleterious to health and fitness. Hypoxic pulmonary hypertension is a particularly serious and maladaptive response to chronic hypoxia, which results from vasoconstriction and pathological remodeling of pulmonary arteries, and can lead to pulmonary edema and right ventricle hypertrophy. We investigated whether deer mice () native to high altitude have attenuated this maladaptive response to chronic hypoxia and whether evolved changes or hypoxia-induced plasticity in pulmonary vasculature might impact ventilation-perfusion (V-Q) matching in chronic hypoxia. Deer mouse populations from both high and low altitudes were born and raised to adulthood in captivity at sea level, and various aspects of lung function were measured before and after exposure to chronic hypoxia (12 kPa O, simulating the O pressure at 4,300 m) for 6-8 wk. In lowlanders, chronic hypoxia increased right ventricle systolic pressure (RVSP) from 14 to 19 mmHg ( = 0.001), in association with thickening of smooth muscle in pulmonary arteries and right ventricle hypertrophy. Chronic hypoxia also impaired V-Q matching in lowlanders (measured at rest using SPECT-CT imaging), as reflected by increased log SD of the perfusion distribution (log SD) from 0.55 to 0.86 ( = 0.031). In highlanders, chronic hypoxia had attenuated effects on RVSP and no effects on smooth muscle thickness, right ventricle mass, or V-Q matching. Therefore, evolved changes in lung function help attenuate maladaptive plasticity and contribute to hypoxia tolerance in high-altitude deer mice.
高海拔地区的缺氧会限制新陈代谢和表现，并可能引发对健康和健身有害的生理调节。低氧性肺动脉高压是对慢性缺氧的一种特别严重和适应不良的反应，它是由肺动脉收缩和病理性重塑引起的，并可导致肺水肿和右心室肥大。我们研究了原产于高海拔地区的鹿鼠（）是否对慢性缺氧的这种适应不良反应具有减弱作用，以及肺血管的进化变化或缺氧诱导的可塑性是否会影响慢性缺氧中的通气-灌注（V-Q）匹配。来自高海拔和低海拔的鹿鼠种群在低海拔地区出生和长大，并在海平面的圈养中成年，然后在暴露于慢性缺氧（12 kPa O，模拟 4300 米处的 O 压力）6-8 周前后测量各种肺功能。在低地居民中，慢性缺氧使右心室收缩压（RVSP）从 14 增加到 19 mmHg（= 0.001），同时肺动脉和平滑肌增厚以及右心室肥大。慢性缺氧还损害了低地居民的 V-Q 匹配（使用 SPECT-CT 成像在休息时测量），反映出灌注分布的对数标准差（log SD）从 0.55 增加到 0.86（= 0.031）。在高地居民中，慢性缺氧对 RVSP 的影响减弱，对平滑肌厚度、右心室质量或 V-Q 匹配没有影响。因此，肺功能的进化变化有助于减弱适应不良的可塑性，并有助于高海拔鹿鼠的缺氧耐受。
