INTEGRATIVE NEUROBIOLOGY OF CARDIOVASCULAR REGULATION

该计划项目资助的重点是心血管调节的综合神经生物学。现在 在它的第36个年头，它代表了爱荷华州心血管研究中心的主要科学重点。 这一竞争性更新的力量是基于其高级领导层的凝聚力和协同作用， 随着新的调查人才的出现，概念和方法不断发展， 从发现机制到将其转化为动物模型和人类的疾病状态。 代表了循环自主控制的三个组成部分的功能集成 四个项目。项目I：终板的神经处理和血液的长期调节 压力（约翰逊，海伊）将确定激活椎板中的中枢神经元的分子决定因素 终末-神经体液驱动启动的关键调节位点。项目II -肾素-血管紧张素- 肥胖-高血压中的醛固酮系统和交感神经激活（Haynes，Mark，Rahmouni） 解决神经体液驱动的两个主要成分与心血管系统的耦合， 即交感神经系统和肾血管紧张素-醛固酮系统作为决定因素 肥胖人群的高血压。项目III -通过酸敏感离子的心血管感觉传导 通道（Abboud，Benson，Welsh）将解决参与机械转导的分子传感器。 压力感受器和化学感受器激活，维持心血管的自主平衡 这对心血管疾病患者的生存至关重要。项目IV -压力感受器中的ROS信号传导 正常和心力衰竭状态下的交感神经元（沙普洛，安德森，韦斯）将重点关注 ROS作为传入（压力感受器）和传出（交感）神经的生理和病理调节剂 激活，在心力衰竭的新模型中具有致命的因果关系。 这五个项目中的分子靶点也反映了与功能靶点相似的整合水平。 心血管感觉器官的神经生物学（如压力化学感受器; 室周器官）;神经体液信号分子（血管紧张素，醛固酮）; 跨膜受体、活性氧物质、分子转导物和通道/通道蛋白。 管理核心、媒介核心和动物模型核心已经提供了宝贵的服务 现有的方案。技术手段先进，动物模型良好， 已确立，以及与病态和致命疾病（如心力衰竭、心肌梗死）的相关性 脑梗死、高血压、动脉粥样硬化、自主神经功能障碍和肥胖是直接的。公共线程创建了 这个计划的知识结构，其中综合成果将远远大于 件.

This Program Project Grant focuses on Integrative Neurobiology of Cardiovascular Regulation. Now n its 36th year, it represents the major scientific emphasis of the Cardiovascular Research Center at Iowa. The strength of this competitive renewal is based on the cohesion and synergy of its senior leadership, its constant evolution in concepts and approaches with new investigative talent, and the continuum of the effort from discovery of mechanisms to their translation into disease states in animal models and humans. The functional integration of the three components of autonomic control of the circulation is represented in four projects. Project I: Neural Processing of the Lamina Terminalis and Long-Term Regulation of Blood Pressure (Johnson, Hay) will identify molecular determinants of activation of central neurons in the lamina terminalis - a key regulatory site for the initiation of neurohumoral drive. Project II - Renin-Angiotensin- Aldosterone System and Sympathetic Activation in Obesity-Hypertension (Haynes, Mark, Rahmouni) will address the coupling of the two major components of neurohumoral drive to the cardiovascular system, namely the sympathetic nervous system and the renal-angiotension-aldosterone system in as determinants of hypertension in obese humans. Project III - Cardiovascular Sensory Transduction by Acid Sensing Ion Channels (Abboud, Benson, Welsh) will address the molecular sensors involved in mechanotransduction of baroreceptors and chemoreceptor activation that maintain an autonomic balance of the cardiovascular system that is essential for survival in cardiovascular disease. Project IV - ROS Signaling in Baroreceptor and Sympathetic Neurons in Normal and Heart Failure States (Chapleau, Anderson, Weiss) will focus on ROS as a physiologic and pathologic modulator of afferent (baroreceptors) and efferent (sympathetic) neural activation, with fatal causal implications in a new model of heart failure. The molecular targets in the five projects also reflect a level of integration similar to the functional ones. There is convergence from the neurobiology of cardiovascular sensory organs (e.g. baro-chemo-receptors; circumventricular organs); to neurohumoral signaling molecules (angiotensin, aldosterone); to transmembrane receptors, reactive oxygen species, molecular transducters, and channels/channel protein. The Administration Core, the Vector Core and Animal Models Core are already providing invaluable service to the existing programs. The technical approaches are state-of-the-art, the animal models are well established, and the relevance to morbid conditions and fatal diseases such as heart failure, myocardial infarction, hypertension, atherosclerosis, dysautonomia, and obesity is direct. Common threads create the intellectual fabric of this program where the integrated outcome will be far greater than the sum of the components.