Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission.
Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission.
复制标题
DOI：
10.14814/phy2.13536
复制
发表时间：
2018-03
影响因子：
2.5
通讯作者：
Stocker SD
中科院分区：
文献类型：
--
作者：
Ferreira CB;Cravo SL;Stocker SD
阻塞性睡眠呼吸暂停（obstructive sleep apnea，OSA）是最常见的睡眠呼吸障碍，与心血管疾病密切相关。在人类中，呼吸暂停增加呼吸努力并提高肌肉交感神经活动（SNA），但SNA激活的主要刺激尚未确定。我们最近开发了一种使用急性气道阻塞的啮齿动物呼吸暂停模型。在这项研究中，我们采用这个模型来测试是否在SNA的海拔是由缺氧，颈动脉化学感受器，或孤束核（NTS）的神经传递介导的。在麻醉的雄性Sprague-Dawley大鼠中，气道阻塞（20 s）增加了膈神经活动（PNA）、动脉血压（ABP）以及腰、肾和内脏SNA。SNA的变化在所有三种交感神经中是相似的。高氧（100%O2）或颈动脉化学感受器去神经手术灭活化学感受器减弱，但没有消除，气道阻塞引起的SNA和ABP的变化。为了中断来自颈动脉化学感受器和颈动脉外传入到后脑的传入信息，在NTS微量注射GABAA激动剂蝇蕈醇或NMDA和非NMDA拮抗剂的混合物之前和之后进行气道阻塞。抑制NTS神经元或阻断多巴胺能受体可减弱腰SNA、内脏SNA、肾SNA和PNA的增加。总的来说，这些研究结果表明，气道阻塞引起的PNA和SNA反应依赖于，部分，在NTS的化学感受器传入和神经递质的神经传递。
Obstructive sleep apnea (OSA) is the most common respiratory disturbance of sleep and is closely associated to cardiovascular diseases. In humans, apnea increases respiratory effort and elevates muscle sympathetic nerve activity (SNA), but the primary stimulus for the SNA activation has not been identified. We recently developed a model of apnea in rodents using acute airway obstruction. In this study, we employed this model to test whether the elevation in SNA was mediated by hypoxia, carotid chemoreceptors, or neurotransmission in the nucleus tractus solitarius (NTS). In anesthetized, male Sprague–Dawley rats, airway obstruction (20s) increased phrenic nerve activity (PNA), arterial blood pressure (ABP), and lumbar, renal, and splanchnic SNA. The changes in SNA were similar across all three sympathetic nerves. Inactivation of chemoreceptors by hyperoxia (100% O2) or surgical denervation of carotid chemoreceptors attenuated, but did not eliminate, the changes in SNA and ABP produced by airway obstruction. To interrupt afferent information from carotid chemoreceptor and extracarotid afferents to the hindbrain, airway obstruction was performed before and after NTS microinjection of the GABAA agonist muscimol or a cocktail of NMDA and non‐NMDA antagonists. Inhibition of NTS neurons or blockade of glutamatergic receptors attenuated the increase in lumbar SNA, splanchnic SNA, renal SNA, and PNA. Collectively, these findings suggest that PNA and SNA responses induced by airway obstruction depend, in part, on chemoreceptors afferents and glutamatergic neurotransmission in the NTS.