CONTROL-RESPIRATORY MODULATION OF SYMPATHETIC ACTIVITY

描述(申请人摘要)：睡眠呼吸暂停综合征很普遍(3-5 占成年人口的百分比)，并与显著的发病率有关 包括高血压。血压升高似乎是由于 基础交感神经活动(SNA)上调。治疗逆转 这种上调监管。我们的理论是，SNA上调的结果是 与睡眠相关的阵发性低氧血症的短期和长期后遗症 呼吸暂停。呼吸系统和心血管系统在 维持动态平衡。SNA的呼吸调节是这方面的一个方面 协调。SNA不仅受呼吸周期的调节，而且 这种调节在短暂的低氧血症期间和之后增加。这个 这种协调的神经底物尚未确定。最近的研究表明 重点研究延髓呼吸调节与神经元间的相互作用 延髓吻侧腹外侧区(RVLM)运动前交感神经元。 然而，桥脑Kolliker-Fuse核(KF)中的神经元 是除了NTS中的那些神经元之外唯一投射到 RVLm和被低氧激活的神经元。我们假设一个直接的 KF呼吸调制神经元之间的桥延体相互作用 RVLM内的核和神经元参与呼吸调节 交感神经活动，这种相互作用是增强 低氧期间和缺氧后交感神经活动的呼吸调节。至 为了验证这一假设，我们提出了一系列神经生理学实验 解决以下具体目标：1)确定是否抑制dl 脑桥活动阻断呼吸一过性和持续性增加 SNA在低氧期间和之后的调节，2)确定是否激活 Dl脑桥增强SNA的呼吸调节，以及3)确定 呼吸调节的KF神经元投射和兴奋RVLM神经元和IF 这些KF神经元在缺氧期间和缺氧后被激活。我们会调查的 控制呼吸和血压的神经底物，瞬变 以及短暂低氧血症对这种控制的持续影响，以及 这种控制受发病率的调节，即高血压的发展。 我们建议在正常大鼠和高血压大鼠以及猫身上进行实验，以 评估dl脑桥对SNA的影响，这种影响的变化 一过性低氧血症和高血压。这些拟议的研究审查了 交感神经活动上调的相关机制 患有睡眠呼吸暂停。

DESCRIPTION (Applicant's abstract): Sleep apnea syndrome is prevalent (3-5 percent of the adult population) and associated with significant morbidity including hypertension. The increased blood pressure appears to result from an up-regulation of basal sympathetic nerve activity (SNA). Treatment reverses this up-regulation. We theorize that the up-regulation of SNA results from both short- and long-term sequelae of episodic hypoxemia associated with sleep apnea. The respiratory and cardiovascular systems are coordinated in the maintenance of homeostasis. Respiratory modulation of SNA is an aspect of this coordination. Not only is SNA modulated with the respiratory cycle but also this modulation increases during and following brief periods of hypoxemia. The neural substrate for this coordination is undefined. Recent studies have focused on neuronal interaction between medullary respiratory-modulated and pre-motor sympathetic neurons of the rostral ventrolateral medulla (RVLM). However, neurons in the dorsolateral (dl) pontine Kolliker-Fuse (KF) nucleus are the only brainstem neurons other than the those in the NTS that project to the RVLM and that are activated by hypoxia. We hypothesize that a direct pontomedullary interaction between respiratory-modulated neurons of the KF nucleus and neurons in RVLM contributes to the respiratory modulation of sympathetic activity and that this interaction underlies the enhanced respiratory modulation of sympathetic activity during and following hypoxia. To test this hypothesis, we propose a series of neurophysiologic experiments addressing the following specific aims: 1) to determine if inhibition of dl pontine activity blocks the transient and sustained increases in respiratory modulation of SNA during and following hypoxia, 2) to determine if activation of dl pons enhances respiratory modulation of SNA, and 3) to determine if respiratory-modulated KF neurons project to and excite RVLM neurons and if these KF neurons are activated during and after hypoxia. We will investigate the neural substrate controlling respiration and blood pressure, the transient and sustained consequences of brief hypoxemia on this control, and the modulation of this control by morbidity, i.e., the development of hypertension. We propose experiments in normo- and hypertensive rats as well as in cats to evaluate the dl pontine influence on SNA, the changes in this influence with transient hypoxemia and hypertension. These proposed studies examine the mechanism of up-regulation of sympathetic nerve activity that is associated with sleep apnea.