CARDIOVASCULAR RESPONSES TO CHRONIC INTERMITTENT HYPOXIA

慢性间歇性缺氧（CIH）是一种广泛使用的重复缺氧模型， 睡眠呼吸暂停综合征患者在睡眠期间发生的低氧血症发作。 期间 在这种呼吸暂停期，缺氧激活化学感受器， 动脉压升高。 在患有睡眠呼吸暂停的人和动物中 暴露于CIH，睡眠期间重复的缺氧期导致 清醒时动脉压升高，结果可能是 交感神经活动水平升高， 急性缺氧 本项目的目标是调查中央 这种持续增加交感神经系统的途径和机制 神经活动 假设CIH导致配体的改变， 去甲肾上腺素能（A2）门控兴奋性和/或抑制性氨基酸受体 孤束核（NTS）中的神经元，因此它们的放电是 与CIH之前相比有所增加。 这些神经元将这种增强的 室旁核交感神经元放电 下丘脑 接受儿茶酚胺能输入的室旁核神经元 包括释放促肾上腺皮质激素释放因子（CRF）作为 发送器 释放CRF的PVN神经元至少部分介导了 CIH后，通过投射到 RVLM和刺激皮质酮释放。 体内和体外 方法将被使用和显微注射，电生理和 分子研究提出了表征突触整合的 化学感受器输入和神经递质的分子调节 受体介导这些整合过程。 具体目标是 旨在评估：1）动脉化学感受器输入的整合， CIH后NTS; 2）A2，去甲肾上腺素能输入的整合 CIH后PVN; 3）CRF系统的功能激活 在CIH之后的PVN内。

Chronic intermittent hypoxia (CIH) is a widely used model for the repetitive bouts of hypoxemia that occur during sleep in sleep apnea patients. During such apneic periods, hypoxia activates chemoreceptors that evoke reflex increases in arterial pressure. In humans with sleep apnea and animals exposed to CIH the repetitive periods of hypoxia during sleep result in tonically increased arterial pressure during waking hours, likely the result of elevated levels of sympathetic nerve activity and an enhanced response to acute hypoxia. The goal of the present project is to investigate the central pathways and mechanisms that underlie this persistent increase in sympathetic nerve activity. It is hypothesized that CIH leads to alterations in ligand gated excitatory and/or inhibitory amino acid receptors in noradrenergic (A2) neurons in the nucleus of the solitary tract (NTS) so that their discharge is increased compared to before CIH. These neurons transmit this enhanced discharge to sympatho-excitatory neuron in the paraventricular nucleus (PVN) of the hypothalamus. PVN neurons receiving the catecholaminergic input include neurons that release corticotropin releasing factor (CRF) as a transmitter. The CRF releasing PVN neurons mediate, at least in part, the enhanced sympathetic discharge observed following CIH via projections to the RVLM and by stimulating corticosterone release. Both in vivo and in vitro approaches will be used and microinjection, electro-physiological and molecular studies are proposed to characterize the synaptic integration of chemoreceptor inputs and the molecular regulation of the neurotransmitter receptors that mediate these integrative processes. The specific aims are designed to assess: 1) The integration of arterial chemoreceptor inputs within the NTS following CIH; 2) The integration of A2, noradrenergic inputs within the PVN following CIH; and 3) The functional activation of the CRF system within the PVN following CIH.