Dept of Physiology and Pharmacology, University of Calgary, Calgary, Canada.
Eur Respir J. 2011 Apr;37(4):880-7. doi: 10.1183/09031936.00156009. Epub 2010 Oct 14.
Erythropoietin (EPO) and soluble EPO receptors (sEPOR) have been proposed to play a central role in the ventilatory acclimatisation to continuous hypoxia in mice. In this study, we demonstrated for the first time in humans (n = 9) that sEPOR is downregulated upon daytime exposure to 4 days of intermittent hypoxia (IH; 6 h·day⁻¹, cycles of 2 min of hypoxia followed by 2 min of reoxygenation; peak end-tidal oxygen tension (P(ET,O₂)) 88 Torr, nadir P(ET,O₂)) 45 Torr), thereby allowing EPO concentration to rise. We also determined the strength of the association between these haematological adaptations and alterations in the acute hypoxic ventilatory response (AHVR). We observed a nadir in sEPOR on day 2 (-70%), concomitant with the peak in EPO concentration (+50%). Following exposure to IH, tidal volume (V(T)) increased, respiratory frequency remained unchanged, and minute ventilation (V'(E)) was increased. There was a negative correlation between EPO and sEPOR (r = -0.261; p = 0.05), and between sEPOR and V(T) (r = -0.331; p = 0.02). EPO was positively correlated with V'(E) (r = 0.458; p = 0.001). In conclusion, the downregulation of sEPOR by IH modulates the subsequent EPO response. Furthermore, the alterations in AHVR and breathing pattern following IH appear to be mediated, at least in part, by the increase in EPO.
促红细胞生成素 (EPO) 和可溶性 EPO 受体 (sEPOR) 被认为在小鼠对持续低氧的通气适应中起核心作用。在这项研究中，我们首次在人类 (n = 9) 中证明，sEPOR 在白天暴露于 4 天间歇性低氧 (IH; 6 h·day⁻¹，2 分钟缺氧后 2 分钟复氧，峰末呼吸气氧分压 (P(ET,O₂)) 88 托，最低 P(ET,O₂)) 45 托）时会下调，从而允许 EPO 浓度升高。我们还确定了这些血液学适应与急性低氧通气反应 (AHVR) 变化之间的关联强度。我们观察到 sEPOR 在第 2 天（-70%）达到最低点，同时 EPO 浓度达到峰值（+50%）。在暴露于 IH 后，潮气量 (V(T)) 增加，呼吸频率保持不变，分钟通气量 (V'(E)) 增加。EPO 与 sEPOR 之间呈负相关（r = -0.261；p = 0.05），sEPOR 与 V(T) 之间呈负相关（r = -0.331；p = 0.02）。EPO 与 V'(E) 呈正相关（r = 0.458；p = 0.001）。总之，IH 下调 sEPOR 调节随后的 EPO 反应。此外，IH 后 AHVR 和呼吸模式的变化似乎至少部分通过 EPO 的增加来介导。
