HYPERTENSION CAUSED BY SLEEP DISORDER BREATHING--NEURAL MECHANISMS

我们的总体目标是确定睡眠障碍的机制， 呼吸（呼吸暂停/呼吸不足和高上气道阻力）导致 持续的日间高血压 我们建议， 睡眠期间间歇性窒息引起的颈动脉化学反射是 睡眠呼吸障碍与白天的主要联系 高血压 致敏性是指细胞周期中 输出相同的刺激水平。 我们的具体目标将 在互补的人类和动物模型中进行研究。 人类研究：首先，我们将确定窒息的急性影响， 上呼吸道高阻力和外周循环兴奋 在睡眠期间使用交感神经肌肉的直接神经内记录 神经活动 其次，我们将确定是否暴露于 间歇性窒息引起化学反射控制敏感化， 肌肉交感神经活动和动脉压。 最后我们 将确定睡眠呼吸障碍是否会导致致敏 化学反射调节交感神经流出和增强 神经性血管收缩 我们将决定 工作人群睡眠障碍所致高血压 通过鼻连续呼吸消除呼吸暂停/呼吸不足/打鼾 气道正压通气 动物研究：在麻醉犬中，颈动脉的关键作用 化学感受器在神经循环敏化间歇性 通过记录单个单位化学感受器来证实窒息 颈动脉窦神经的传入活动和多单位传出 肾和肾上腺神经的活动。 在未麻醉的狗中， 颈动脉窦的隔离灌注，我们将确定是否 在没有全身性窒息的情况下发生化学反射敏化。 在未麻醉的狗中，我们将评估化学反射诱导的 肾上腺素分泌增加神经源性血管收缩。 我们的实验将明确睡眠呼吸障碍 和高血压。 这一定义将反过来导致一个更合理的 治疗方法，并确定另一类高血压， 已知的发病机制。

Our overall goal is to determine the mechanism whereby sleep disordered breathing (apnea/hypopnea and high upper airway resistance) causes sustained daytime hypertension. We propose that sensitization of the carotid chemoreflex by intermittent asphyxia during sleep is the principal link between sleep disordered breathing and daytime hypertension. Sensitization refers to a time-dependent increase in efferent output for the same level of stimulus. Our specific aims will be pursued in complementary human and animal models. Human studies: First, we will determine the acute effects of asphyxia, high upper airway resistance and arousal on the peripheral circulation during sleep using direct intraneural recordings of muscle sympathetic nerve activity. Secondly, we will determine whether exposure to intermittent asphyxia causes sensitization of chemoreflex control of muscle sympathetic nerve activity and arterial pressure. Finally, we will determine whether sleep disordered breathing causes sensitization of chemoreflex regulation of sympathetic outflow and augmented neurogenic vasoconstriction. We will determine the proportion of hypertension in a working population attributable to sleep disordered breathing by eliminating apnea/hypopnea/snoring with nasal continuous positive airway pressure. Animal studies: In anesthetized dogs, the critical role of the carotid chemoreceptor in the neurocirculatory sensitization to intermittent asphyxia will be demonstrated by recording single unit chemoreceptor afferent activity in the carotid sinus nerve and multiunit efferent activity in the renal and adrenal nerves. In unanesthetized dogs with isolated perfusion of the carotid sinus we will determine whether chemoreflex sensitization occurs in the absence of systemic asphyxia. In unanesthetized dogs, we will evaluate the role of chemoreflex-induced epinephrine secretion in augmenting neurogenic vasoconstriction. Our experiments will define the link between sleep disordered breathing and hypertension. This definition will, in turn, lead to a more rational approach to therapy and identify another category of hypertension with a known pathogenesis.