CRCNS: Modeling the respiratory-sympathetic coupling in neurogenic hypertension

过度的交感神经活动在高血压的发生和维持中起着至关重要的作用。 在患有阻塞性睡眠呼吸暂停(OSA)的高血压患者中可以观察到这种自主神经功能障碍。 OSA患者长期暴露于间歇性低氧(CIH)是导致交感神经兴奋的主要因素 过度活动和高血压。CIH推动的共鸣产出的增长在很大程度上取决于 出现主动呼气模式。呼吸中枢模式发生器(RCPG)由两部分组成 相互作用的振荡器。第一种占据B6tzinger/Pre-B6tzinger复合体，并产生自持的 呼吸节律控制横隔膜提供吸气。第二个振荡器，副面振荡器 呼吸群(PFRG)位于斜方体后核(RTN)。出现了RTN/pFRG振荡 在低氧和高碳酸血症条件下，驱动运动输出到腹肌以供活动(强迫) 过期了。这些呼吸回路与吻侧和尾侧交感神经元的相互作用 延髓腹外侧区在交感神经传出驱动中引起呼吸相关的振荡。接触三氯甲烷 导致突触中rtn/pFRG神经元群体的兴奋性改变和/或修饰 呼吸振荡器和交感神经元之间的联系，最终导致 基线交感神经活动和动脉压。这个跨学科的项目旨在揭示 在健康和疾病中，大脑中呼吸和血压控制的机制，以及 第一次将它们转化为现实的计算模型。这样的模式将会有前所未有的 可能产生有效的非药物手段来控制血压和呼吸 植入式生物反馈装置(如迷走神经刺激)和用于引导控制的非侵入性装置 自主神经功能(例如，设备引导的起搏呼吸)。此外，它将提供强大的科学 评价替代和补充医学干预措施的有用性和安全性的基础； 例如控制呼吸练习(例如，通过冥想和瑜伽)，用于降低血压和 改善心率变异性。

Excessive sympathetic activity plays a crucial role in the development and maintenance of hypertension. Such autonomic dysfunction is observed in hypertensive patients with obstructive sleep apnea (OSA). Chronic exposure to intermittent hypoxia (CIH) that occurs in OSA is the main factor leading to sympathetic overactivity and hypertension. A CIH-driven increase in sympathetic output is largely dependent on the emergence of active expiratory pattern. The respiratory central pattern generator (rCPG) is composed of two interacting oscillators. The first occupies B6tzinger/pre-B6tzinger complexes and generates self-sustained respiratory rhythm controlling the diaphragm to provide inspiration. The second oscillator, the parafacial respiratory group (pFRG), resides in the retrotrapezoid nucleus (RTN). The RTN/pFRG oscillations emerge in hypoxic and hypercapnic conditions, and drive motor output to abdominal muscles for active (forced) expiration. Interactions of these respiratory circuits with the sympathetic neurons ofthe rostral and caudal ventrolateral medulla evoke respiratory-related oscillations in sympathetic efferent drive. Exposure to CIH leads to alterations in excitability of RTN/pFRG neuronal population and/or modiflcations in synaptic connections between respiratory oscillators and sympathetic neurons which ultimately results in the elevated baseline sympathetic activity and arterial pressure. This interdisciplinary project aims to reveal the mechanisms that couple breathing and control of blood pressure in the brain in health and disease, and for the first time translate them into a realistic computational model. Such a model will have the unprecedented potential for generating effective non-pharmacological means of controlling blood pressure and breathing via implantable biofeedback devices (e.g. vagus nerve stimulation) and non-invasive devices for guided control of autonomic function (e.g. device-guided paced respiration). Furthermore, it will provide a robust scientific substrate for evaluating the usefulness and safety of alternative and complementary medicine interventions, such as controlled breathing practices (e.g. through meditation and yoga), for lowering blood pressure and improving heart rate variability.