Sympathetic activation by intermittent hypoxia

描述（由申请人提供）： 脑桥腹外侧区在脑卒中后短期抑郁（STD）中起着关键作用。 缺氧后的呼吸频率;和血清素，以及一氧化氮 氧化物，在长时程促进（LTF）的发展中发挥作用 因为反复缺氧GABAa受体亚单位 控制交感神经激活（SNA）的脑桥延髓回路， 膈神经活动（PNA）显示mRNA的差异表达， 缺氧条件反射我们的数据表明， SNA不仅在减少的制备中发生， （增加）并在一定程度上改变其激活模式。 在短暂缺氧期间和之后的呼吸周期。因此我们 假设SNA的上调是由于神经系统的可塑性， 呼吸神经系统与重复缺氧事件相关，一项研究 设计称为条件反射。为了验证这一假设，我们提出了一系列 神经生理学和分子生物学实验，解决以下问题 具体目标：1）区分中枢机制与外周机制 潜在的SNA增加后，条件反射，2）相关的 短时程增强和抑制（STD）以及长时程易化 (LTF)膈神经活动（PNA）明显，SNA变化，以及3） 表征GABAa受体亚单位在脑内的时间表达， 在本研究设计中，控制SNA和PNA的脑干核团，以及4） 比较CIH条件化在两种不同啮齿动物品系中的作用， 对缺氧和一氧化氮合成酶抑制剂的反应。这种方法 提供了一个机会，以确定这些动物是否发展增加 SNA与缺氧反应的比例，以及 交感神经和呼吸控制可塑性。这些研究建议 检查与上调相关的神经生理学和分子机制， SNA活性的变化，这似乎发生在临床条件下 与反复缺氧有关;例如，睡眠呼吸暂停与充血性心脏病 失败

DESCRIPTION (provided by applicant): The ventrolateral pons plays a key role in the short-term depression (STD) in respiratory frequency following hypoxia; and serotonin, as well as nitric oxide, play a part in the development of long-term facilitation (LTF) following repetitive bouts of hypoxia. GABAa-receptor sub-units in the pontomedullary circuits controlling sympathetic nerve activation (SNA) and phrenic nerve activity (PNA) show differential expression of mRNA following conditioning with hypoxia. Our data indicate that respiratory modulation of SNA not only occurs in a reduced preparation but also quantitatively (increases) and quantitatively changes its activation pattern within a breathing cycle during and following brief periods of hypoxia. Thus, we hypothesize that the up-regulation of SNA results from plasticity in the respiratory neural systems associated with repetitive hypoxic events, a study design called conditioning. To test this hypothesis, we propose a series of neurophysiologic and molecular biologic experiments addressing the following specific aims: 1) to differentiate central versus peripheral mechanisms underlying the increases in SNA following conditioning, 2) to correlate the short-term potentiation and depression (STD) as well as long-term facilitation (LTF) evident in phrenic nerve activity (PNA) with changes in SNA, and 3) to characterize the temporal expression of subunits of GABAa receptors in the brainstem nuclei controlling SNA and PNA in this study design, and 4) to compare the effects of CIH conditioning in two rodent strains with different responses to hypoxia and to nitric oxide synthetase inhibitors. This approach provides an opportunity to determine whether these animals develop increased SNA in proportion to the hypoxic response, and the interrelationship of sympathetic and respiratory control plasticity. These proposed studies examine neurophysiologic and molecular mechanisms relevant to the up-regulation of SNA activity which seems to occur in clinical conditions associated with repetitive hypoxia; e.g., sleep apnea and congestive heart failure.