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/低呼吸和上呼吸道阻力高)引起 持续的白天高血压。我们建议，敏化 睡眠中间歇性窒息引起的颈动脉化学反射是 睡眠呼吸障碍和白天之间的主要联系 高血压。敏化指的是随着时间的推移， 相同刺激水平的传出产出。我们的具体目标将是 在互补的人类和动物模型中进行研究。 人体研究：首先，我们将确定窒息的急性影响， 上呼吸道阻力高，外周循环唤醒 在睡眠中使用神经内直接记录肌肉交感神经 神经活动。其次，我们将确定是否接触到 间歇性窒息引起化学反射控制的敏化 肌肉交感神经活动和动脉压。最后，我们 将决定睡眠呼吸障碍是否会导致敏感化 交感神经流出的化学反射调节及其增强 神经性血管收缩。我们将确定以下比例： 工作人群中的高血压可归因于睡眠障碍 用鼻腔持续呼吸消除呼吸暂停/低呼吸/鼾声 气道正压。 动物研究：在麻醉的狗身上，颈动脉的关键作用 化学感受器在神经循环对间歇性敏感性中的作用 通过记录单个单位的化学感受器来证实窒息 颈动脉窦神经和多单位传出的传入活动 肾神经和肾上腺神经的活动。在未麻醉的狗身上 颈动脉窦的隔离灌流我们将确定 化学反射敏感化发生在没有全身性窒息的情况下。 在未麻醉的狗身上，我们将评估化学反射诱导的作用 肾上腺素分泌增强神经源性血管收缩。 我们的实验将确定睡眠呼吸障碍之间的联系 还有高血压。这一定义将反过来导致更合理的 治疗方法和识别另一类高血压 这是一种已知的发病机制。

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.