Reactive oxygen species (ROS) are proposed as mediators of chronic intermittent hypoxia (CIH)-induced respiratory plasticity. We sought to determine if NADPH oxidase 2 (NOX2)-derived ROS underpin CIH-induced maladaptive changes in respiratory control. Adult male mice (C57BL/6 J) were assigned to one of three groups: normoxic controls (sham); chronic intermittent hypoxia-exposed (CIH, 12 cycles/hour, 8 h/day for 14 days); and CIH + apocynin (NOX2 inhibitor, 2 mM) given in the drinking water throughout exposure to CIH. In addition, we studied sham and CIH-exposed NOX2-null mice (B6.129S-Cybb^TM1Din/J). Whole-body plethysmography was used to measure breathing and metabolic parameters. Ventilation (V̇_I/V̇CO₂) during normoxia was unaffected by CIH, but apnoea index was increased, which was prevented by apocynin, but not by NOX2 deletion. The ventilatory response to hypercapnia following exposure to CIH was potentiated in NOX2-null mice. Our results reveal ROS-dependent influences on the control of breathing and point to antioxidant intervention as a potential adjunctive therapeutic strategy in respiratory control disorders.

活性氧 (ROS) 被提议作为慢性间歇性缺氧 (CIH) 诱导的呼吸可塑性的介质。我们试图确定 NADPH 氧化酶 2 (NOX2) 衍生的 ROS 是否支持 CIH 诱导的呼吸控制适应不良变化。成年雄性小鼠 (C57BL/6 J) 被分配到以下三组之一：常氧对照组（假）；慢性间歇性缺氧暴露（CIH，12 个周期/小时，8 小时/天，持续 14 天）；和 CIH + 夹竹桃麻素（NOX2 抑制剂，2 mM）在暴露于 CIH 的整个过程中在饮用水中给予。此外，我们研究了假和 CIH 暴露的 NOX2-null 小鼠 (B6.129S- Cybb ^{TM1Din /J} )。全身体积描记法用于测量呼吸和代谢参数。通风 ( V̇ _I / V̇ CO ₂) 在常氧期间不受 CIH 影响，但呼吸暂停指数增加，这可以通过夹竹桃麻素来预防，但 NOX2 缺失不会。在 NOX2-null 小鼠中，暴露于 CIH 后对高碳酸血症的通气反应增强。我们的结果揭示了 ROS 对呼吸控制的影响，并指出抗氧化干预是呼吸控制障碍的潜在辅助治疗策略。