CARDIOVASCULAR RESPONSES TO CHRONIC INTERMITTENT HYPOXIA

慢性间歇性低氧(CIH)是一种广泛使用的重复低氧模型 睡眠呼吸暂停患者睡眠期间出现的一连串低氧血症。在.期间 在这样的窒息期间，缺氧会激活化学感受器，从而唤起反射 动脉压升高。患有睡眠呼吸暂停的人和动物 暴露在CIH中，睡眠中重复缺氧的时间会导致 清醒时强直的动脉压升高，可能是 交感神经活动水平的升高和对 急性缺氧。本项目的目标是调查中央 交感神经持续增加的途径和机制 神经活动。假设CIH会导致配体的改变 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前相比有所增加。这些神经元将这种增强的信息传递给 向室旁核(PVN)交感兴奋神经元的放电 下丘脑。接受儿茶酚胺能传入的下丘脑室旁核神经元 包括释放促肾上腺皮质激素释放因子(CRF)的神经元 发射机。释放CRF的下丘脑室旁核神经元至少部分地介导了 脑出血后交感神经放电增强通过投射至 RVLM和刺激皮质酮的释放。无论是体内还是体外 将使用微注射、电生理和 分子研究被建议用来描述突触整合。 化学感受器输入与神经递质的分子调控 调节这些整合过程的受体。具体目标是 旨在评估：1)动脉化学感受器输入的整合 CIH后的NTS；2)内A2、去甲肾上腺素能输入的整合 (3)CRF系统的功能激活。 在CIH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.