PERIPHERAL AND CENTRAL VENTILATORY CONTROL

描述(改编自申请人的摘要)：长期目标 本课题旨在进一步阐明黄曲霉病菌的控制机制。 呼吸。具体地说，这个项目的重点是控制吸入 低氧与肺通气量时间依赖性增加的机制 关于长期低氧暴露，称为低氧习服(VAH) 以及维持过度换气的机制。 暴露在低氧环境中(去习服)。这个项目的大部分内容都涉及 引起氧敏感器官--颈动脉--敏感性增加的机制 机体(CBS)，对VAH期间的低氧。具体目标是：1. 确定抑制性CB多巴胺(DA)受体是否在 哇。2.确定提供给CB的过量DA是否会阻止VAH。3. 以确定抑制性DA机制是否可以人工诱导 加速VAH。4.确定CB中兴奋性DA受体是否 在VAH期间上调。5.确定一氧化氮(NO)是否是一种 山羊CB的抑制性调节剂。6.确定是否没有 CB中的合成酶一氧化氮合酶(NOS)受到抑制 在VAH过程中，CB对低氧的敏感性增加 刺激。7.检验中枢化学感受器是 在VAH期间重置，从而负责维持过度换气 在脱习服期间。独特的清醒山羊制剂，允许 慢性阻塞性肺疾病药物疗效评价及血气刺激隔离 将使用CB。这些研究将由CB的录音支持 麻醉山羊的传入神经活动。DA的功能 CB中的受体和化学介体将在正常氧气下进行评估 水平和在急性和长期缺氧期间使用组织化学， 免疫细胞化学、放射自显影和原位杂交。这些 研究将提供有关哥伦比亚广播公司职能的新信息，这些信息包括 在保护个人免受缺氧性状态的伤害方面很重要 反射增加了呼吸。在某些病理条件下 刺激可能会导致呼吸困难。对它们的功能的了解是 对了解疾病的呼吸道病理生理学至关重要 以急性和慢性缺氧为特征，如慢性梗阻性 肺部疾病和睡眠呼吸暂停。这些研究也将增加我们的 接触铅作业的正常人对呼吸控制的认识 缺氧，例如，上升到高海拔。

DESCRIPTION (Adapted from the applicant's abstract): The long term goal of this project is to further elucidate mechanisms of the control of respiration. Specifically, this project focuses on control of breathing in hypoxia and mechanisms producing the time-dependent increase in ventilation on exposure to prolonged hypoxia, termed acclimatization to hypoxia (VAH) and the mechanisms maintaining the hyperventilation on termination of the exposure to hypoxia (de-acclimatization). Much of the project deals with mechanisms causing increased sensitivity of O2 sensing organs, the carotid bodies (CBs), to hypoxia during VAH. The specific aims are: 1. To determine if inhibitory CB dopamine (DA) receptors are down-regulated during VAH. 2. To determine if excess DA provided to the CB will prevent VAH. 3. To determine if inhibitory DA mechanisms can be artificially induced to accelerate VAH. 4. To determine if excitatory DA receptors in the CB are up-regulated during VAH. 5. To determine if nitric oxide (NO) is an inhibitory modulator of the goat CB. 6. To determine if the NO synthesizing enzyme in the CB, nitric oxide synthase (NOS), is inhibited during VAH resulting in increased sensitivity of the CB to hypoxic stimulation. 7. To test the hypothesis that central chemoreceptors are reset during VAH and thus responsible for maintaining hyperventilation during de-acclimatization. Unique awake goat preparations that allow assessment of drug effects at the CB and isolation of blood gas stimuli to the CB will be used. These studies will be supported by recordings of CB afferent neural activity in anesthetized goats. The function of DA receptors and chemical mediators in the CB will be assessed under normal O2 levels and during acute and prolonged hypoxia using histochemistry, immunocytochemistry, autoradiography and in situ hybridization. These studies will provide new information on function of the CBs, which are important in defending the individual against hypoxic states by causing reflex increased breathing. Under certain pathologic conditions CB stimulation may contribute to dyspnea. Knowledge of their function is critical to understanding of the respiratory pathophysiology of diseases characterized by acute and chronic hypoxia such as chronic obstructive pulmonary disease and sleep apnea. The studies will also add to our understanding of the control of respiration in normal individuals exposed to hypoxia, e.g., ascent to high altitude.