INTEGRATIVE FUNCTIONS IN NEUROVASCULAR CONTROL--PPG

在这个请求中，我们重点关注三个密切相关的主题。第一 解决了压力反射的中央调解，该反射检查 臂旁核的整合作用；神经递质功能 兴奋性氨基酸；以及大脑5-羟色胺系统在肾脏中的作用 和心血管调节。第二个主题是关于内皮细胞-- 神经-血管相互作用与3个检查旁分泌的子项目 力电效应对压力感受器的影响及其机制 内源性神经营养因子、一氧化氮和S-亚硝硫醇的作用 调节交感神经功能；旁分泌调节血管 动脉粥样硬化模型中的音调。第三个主题涉及Reflex 在选定的生理和病理状态下的自主神经控制 关于压力感受器反射个体发育和差异的动物亚项目 对肾脏功能成分的交感神经控制；以及另外两个 人类的子项目，一个关于反射性神经血管控制的子项目 等长运动，以及关于异常自主神经控制机制的研究 随着年龄的增长和睡眠呼吸暂停。三个有效规划和建立 核心将为整个计划提供服务。我们相信这份申请 对A委员会的批评作出直接和全面的回应 几个优点：1)它是更专注的离子神经控制，具有 是我们研究的强项；2)它汇集了几位资深学生 来自六个部门的具有各种专业知识的调查人员(医学、 神经学、解剖学、药理学、儿科学和妇产科) 在一起很多年了；3)从 研究分离的细胞到系统、动物模型和人类；4)它 突出了该团队将基本概念带入 在一个优秀的科学互动中人类调查的舞台 环境；5)它揭示了调查的特殊记录- 托尔斯。我们有信心，总的结果会好于总和 所有的零件。

In this request, we focus on 3 tightly related themes. The first addresses Central Mediation of the Baroreflex that examines the integrative role of parabrachial nucleus; neurotransmitter functions of excitatory amino acids; and role of the brain serotonin system in renal and cardiovascular adjustments. The second theme addresses Endothelial-- Neural-Vascular Interactions with 3 subprojects that examine paracrine influences on baroreceptors and mechanisms of mechanoelectrical transduction; role of EDRF, nitric oxide (NO), and S-nitrosothiols (NOF) in regulating sympathetic function; and paracrine modulation of vascular tone in a model of atherosclerosis. The third theme addresses Reflex Autonomic Control in Selected Physiologic and Pathologic States with two subprojects in animals on the ontogeny of baroreflex and the differential sympathetic control of functional components of the kidney; and two other subprojects in humans, one on reflex neurovascular control during isometric exercise, and one on mechanisms of abnormal autonomic control with aging and sleep apnea. Three efficiently planned and established Cores will serve the entire program. We believe this application responds directly and fully to the criticisms of Committee A. It has several strengths: 1) it is more focused ion neural control which has been the forte of our research; 2) it brings together several senior investigators with various expertise from six Departments (Medicine, Neurology, Anatomy, Pharmacology, Pediatrics and Ob-Gyn) who have worked together for many years; 3) it is much more integrative extending from work on isolated cells to systems, to animal models and to humans; 4) it highlights the unique ability of this group to bring basic concepts into the arena of human investigation in an excellent scientific interactive environment; 5) it reveals the exceptional track record of the investiga- tors. We are confident the overall outcome will be better than the sum of the parts.