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），并与显著的发病率相关 包括高血压。血压升高似乎是由于 基底交感神经活性（SNA）的上调。治疗逆转 这种上调。我们推测SNA的上调是由两种因素共同作用的结果。 睡眠相关的发作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是协调的， 维持体内平衡。SNA的呼吸调节是其中的一个方面 协同SNA不仅受呼吸周期的调节， 这种调节在低氧血症的短暂时期期间和之后增加。的 这种协调的神经基质是不确定的。最近的研究 集中在延髓神经元之间的相互作用， 延髓头端腹外侧区（RVLM）的前运动交感神经元。 然而，在背外侧（dl）脑桥Kolliker-korney（KF）核的神经元， 是唯一的脑干神经元以外的那些在NTS的项目， RVLM和由缺氧激活。我们假设一个直接的 KF神经元间的相互作用 RVLM中的核和神经元有助于呼吸调制， 交感神经活动，这种相互作用是增强 在缺氧期间和之后交感神经活动的呼吸调节。到 为了验证这一假设，我们提出了一系列的神经生理学实验 解决以下具体目的：1）确定是否抑制DL 脑桥活动阻断了短暂和持续的呼吸增加， 在缺氧期间和缺氧后SNA的调节，2）确定激活是否 增强SNA的呼吸调节，以及3）确定是否 调制的KF神经元投射到并激发RVLM神经元，如果 这些KF神经元在缺氧期间和之后被激活。我们将调查 控制呼吸和血压的神经基质， 短暂低氧血症对该对照的持续影响， 通过发病率调节这种控制，即，高血压的发展。 我们建议在正常和高血压大鼠以及猫中进行实验， 评估dl脑桥对SNA的影响， 短暂低氧血症和高血压。这些拟议的研究审查了 相关交感神经活动上调的机制 睡眠呼吸暂停综合症

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.