Departamento de Fisiologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
J Appl Physiol (1985). 2020 Jul 1;129(1):163-172. doi: 10.1152/japplphysiol.00811.2019. Epub 2020 Jun 18.
Obstructive sleep apnea (OSA) is often associated with sympathetic overactivity and hypertension. These associations are mainly attributed to hypoxia acting on arterial chemoreceptors. However, the contribution of arousal from sleep is unclear. We measured the effect of OSA and sleep fragmentation on cardiovascular and sympathetic function and gene expression in the brain in rats. Male Wistar rats were fitted with a tracheal balloon and EEG and electromyogram electrodes and assigned to control ( = 6), OSA ( = 9), or arousal ( = 8) treatments. The OSA group was subjected to obstructive apnea, each time the rat entered sleep, for 8 h/day for 15 days. The arousal group was similarly exposed to vibration, which was produced with a miniature vibration motor mounted on the rat's head. Vibration intensity slowly increased until the rat awoke. One day after the last apnea or arousal, rats were anesthetized and arterial blood pressure and splanchnic sympathetic nerve activity (SSNA) were recorded. Baseline mean and diastolic pressure were increased after OSA. Resting SSNA was similar in the three groups, but both OSA and sleep fragmentation increased sympathetic activation in response to airway obstruction and chemoreflex activation by cyanide. OSA increased superoxide dismutases 1 and 2 in the brainstem, whereas sleep fragmentation did not. Our results suggest that sympathetic overactivity to chemoreceptor stimulation was a consequence of arousal from sleep. Our study suggests that sleep disruption may have an important role in the development of apnea-related sympathetic activation. Obstructive sleep apnea causes a hyperactive chemoreflex, with increased sympathetic activation. However, it is not clear whether this pathophysiologic mechanism is due to repeated hypoxia or to sleep disruption. The present study suggests that sleep fragmentation contributes importantly to increased sympathetic activation after chemoreceptor stimulation. This suggests that sleep fragmentation has an important role in the sympathetic activation seen in sleep apnea patients.
阻塞性睡眠呼吸暂停（OSA）常与交感神经过度活跃和高血压相关。这些关联主要归因于缺氧作用于动脉化学感受器。然而，睡眠中觉醒的贡献尚不清楚。我们测量了 OSA 和睡眠片段化对大鼠心血管和交感神经功能以及大脑基因表达的影响。雄性 Wistar 大鼠被安置气管球囊和 EEG 及肌电图电极，并分配到对照组（n = 6）、OSA 组（n = 9）或觉醒组（n = 8）。OSA 组接受阻塞性呼吸暂停，每次大鼠进入睡眠时，每天持续 8 小时，共 15 天。觉醒组则类似地暴露于振动中，振动通过安装在大鼠头部的微型振动马达产生。振动强度逐渐增加，直到大鼠醒来。最后一次呼吸暂停或觉醒后的一天，大鼠被麻醉，记录动脉血压和内脏交感神经活动（SSNA）。OSA 后，基线平均压和舒张压增加。三组大鼠的静息 SSNA 相似，但 OSA 和睡眠片段化均增加了对气道阻塞和氰化物化学感受器激活的交感神经激活。OSA 增加了脑干中超氧化物歧化酶 1 和 2，而睡眠片段化则没有。我们的结果表明，化学感受器刺激的交感神经过度活跃是睡眠中觉醒的结果。我们的研究表明，睡眠中断可能在与呼吸暂停相关的交感神经激活的发展中起重要作用。阻塞性睡眠呼吸暂停导致化学感受器反射过度活跃，交感神经激活增加。然而，目前尚不清楚这种病理生理机制是由于反复缺氧还是睡眠中断引起的。本研究表明，睡眠片段化在化学感受器刺激后交感神经激活的增加中起重要作用。这表明睡眠片段化在睡眠呼吸暂停患者中看到的交感神经激活中起着重要作用。
