Conference on Autonomic Regulation of Cardiovascular Function in Health and Disea

健康与疾病中心血管功能自主调节会议

• 批准号: 8385060
• 负责人: Martin Frank
• 金额: $ 0.5万
• 依托单位: AMERICAN PHYSIOLOGICAL SOCIETY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-03 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8385060
• 关键词: American; Angiotensin II; Animals; Area; Autonomic nervous system disorders; Basic Science; Blood Circulation; Blood flow; Cardiac; Cardiac Output; Cardiovascular Physiology; Cardiovascular system; Cells; Chronic; Clinical; Communities; Data; Denervation; Development; Devices; Diabetes Mellitus; Disease; Drug resistance; Effectiveness; Endocrine; Equilibrium; Essential Hypertension; Fostering; Functional disorder; Gene Proteins; Generations; Glutamates; Health; Heart failure; Human; Hypertension; Hypothalamic structure; International; Intervention; Ion Channel; Kidney; Mediator of activation protein; Membrane; Metabolic Diseases; Metabolic syndrome; Mind; Molecular; Molecular Genetics; Mus; Nerve; Neuraxis; Nitric Oxide; Obesity; Oral; Organ; Outcome; Oxidative Stress; Panic Disorder; Pathogenesis; Pathology; Patients; Peripheral Resistance; Physiological; Physiology; Postdoctoral Fellow; Pressoreceptors; Property; Recording of previous events; Reflex action; Refractory; Regulation; Renin; Research; Research Personnel; Role; Signal Pathway; Signal Transduction; Societies; Subfornical Organ; Superoxide Dismutase; Sympathetic Nervous System; System; Techniques; Therapeutic Studies; Time; Transcriptional Regulation; Transfection; Translational Regulation; Translations; Uncertainty; Underrepresented Minority; Vascular resistance; Work; autocrine; carotid sinus; gamma-Aminobutyric Acid; graduate student; improved; meetings; nanoparticle; neuromechanism; novel; oxidant stress; paracrine; posters; pressure; programs; receptor; symposium; tool; translational approach; vector

DESCRIPTION (provided by applicant): Specific Aims Over the past 100 years we have acquired a comprehensive understanding of the neural mechanisms that regulate arterial pressure and peripheral resistance. In the past 20 years we have elucidated many cellular and molecular mechanisms that control sympathetic nerve activity. Much of this work has been driven by a lack of understanding of the mechanisms responsible for the development of essential hypertension. There is little doubt that augmented sympathetic nerve activity contributes to the pathogenesis of a variety of disease states including hypertension, heart failure, diabetes and panic disorders. We now have the capability to understand discrete molecular mechanisms responsible for altering sympathetic nerve activity in disease states. These mechanisms alter specific ion channel function and membrane properties in order to evoke sympatho-excitation. Current therapy for hypertension and heart failure, in large part, target the sympathetic nervous system and the renin- angiotensin II system (RAS). The effectiveness of these therapies is due to the intense activation of these systems. Unfortunately, these treatment paradigms have not changed for many years. In spite of the fact that new pharmacological therapies have slightly improved outcomes in recent years a large segment of patients are refractory to these treatments. This fact has prompted the scientific community to investigate new targets for pharmacological intervention and to look to device therapy for hypertension and heart failure. Examples of the latter are renal sympathetic nerve denervation and carotid sinus baroreceptor stimulation for treatment of patients with drug-resistant hypertension. Furthermore, the utilization of novel vectors for the delivery of proteins and genes to discrete areas of autonomic regulation and the advent of chronic recording techniques of physiological parameters has, more than any other time in history, provided the tools to discover new targets for therapy. An example of the latter is the demonstration by Lindley and coworkers (Circulation Research 94:402-409, 2004; Am. J. Physiol. 296:R1-R8. 2009) that transfection of the subfornical organ with superoxide dismutase in mice with heart failure, not only reduces sympathetic nerve activity but actually improves cardiac function. New nanoparticle delivery techniques can be utilized for targeted therapy to the central nervous system for the treatment of diseases characterized by sympathoexcitation. This American Physiological Society (APS) conference will focus on many of these mechanisms. Sessions will include the role of autocrine, paracrine and endocrine mediators of reflexes and areas of the central nervous system that are known to regulate sympathetic function (e.g. the hypothalamus and medulla). Symposia and poster presentations will focus on reactive oxidant stress, nitric oxide, angiotensin II, angiotensn (1-7), glutamate, GABA and the transcriptional and translational regulation of the receptors for many of these mediators. The areas of research to be discussed at this conference are pivotal to a translational approach in the treatment and management of primary autonomic disorders and to those evolving from cardiovascular and/or metabolic diseases. The melding of human, animal, cellular and molecular physiology will foster discussion of additional integrative approaches in this area of biomedicine. With the above in mind, the specific aims of the proposed conference are: 1. Bring together leaders in the field of autonomic cardiovascular physiology and pathophysiology for an intense discussion of the current research and therapy related to sympathoexcitation in a variety of disease states. 2. Provide a venue for junior investigators, graduate students and post-doctoral fellows to highlight their research in the form of oral and poster presentations. 3. Foster the generation of new ideas targeted to the translation of basic science into clinical therapies. 4. Establish new relationships between investigators in the area of autonomic regulation of cardiovascular function. 5. Provide an international forum in which underrepresented minorities can participate. PUBLIC HEALTH RELEVANCE: The purpose of this conference is to provide a scientific forum for the exchange of ideas and the presentation of the most recent data on the regulation of sympathetic nerve activity in health and disease. Sympathetic activation, while considered a physiologically relevant and important regulator of arterial pressure, blood flow and vascular resistance, is thought to contribute to pathology, if overactive. This is especially true in those conditions that require a high level of sympathetic tone to compensate for an abnormal cardiac output or where sympathetic nervous activity sustains arterial pressure in a range that is clearly detrimental to organ function. It is critical that a comprehensive understanding of the integrative mechanisms that take part in abnormal sympathetic function take place so that more rational therapy for these disorders can be developed. In this conference we will specifically focus on disorders that have been characterized as involving abnormalities in sympathetic regulation. The meeting will take an integrative approach to understanding sympathetic regulation and will incorporate genetic, molecular, cellular and whole animal approaches to the topics covered in this conference. There has never been an APS conference on this topic. The program will incorporate several topics related to sympathetic activation. These will include symposia related to central autocrine, paracrine and endocrine influences. New data on the ACE-ACE2 balance and central cellular signaling pathways will be covered. Oxidative stress is now thought to be part of normal cell signaling and in excess to contribute to activation of excitable cells and contribute to pathology. At least 1 symposium and several talks will be dedicated to sympathetic regulation in humans. These talks will include heart failure, hypertension, POTS, panic disorder and obesity/metabolic syndrome.

描述（由申请人提供）：在过去的100年中，具体目标我们对调节动脉压和外周抗性的神经机制有了全面的了解。在过去的20年中，我们阐明了控制交感神经活性的许多细胞和分子机制。这项工作的大部分是由于缺乏对基本高血压发展的机制的理解所驱动的。毫无疑问，增强的交感神经活动有助于多种疾病状态的发病机理，包括高血压，心力衰竭，糖尿病和恐慌症。现在，我们有能力理解负责改变疾病状态中交感神经活动的离散分子机制。这些机制改变了特定的离子通道功能和膜特性，以引起交感神经激发。当前针对高血压和心力衰竭的治疗在很大程度上是针对交感神经系统和重素血管紧张素II系统（RAS）的。这些疗法的有效性是由于这些系统的强烈激活。不幸的是，这些治疗范式多年来没有改变。尽管近年来，新的药理学疗法的预后略有改善，但大部分患者对这些治疗是难治性的。这一事实促使科学界调查了药理学干预的新目标，并寻找用于高血压和心力衰竭的设备治疗。后者的例子是肾交感神经去神经和颈动脉鼻窦刺激，用于治疗耐药性高血压患者。此外，新型向量用于传递蛋白质和基因来分散自主神经调节领域以及生理参数的慢性记录技术的出现，比历史上的任何其他时间都多，提供了发现新目标的工具。后者的一个例子是Lindley及其同事的演示（循环研究94：402-409，2004;Am。J.Physiol。296：R1-R8。2009）表明，在患有心力衰竭的小鼠中，用超氧化物歧化酶转染了心脏衰竭，不仅会减少交感神经能力的副作用，而且实际上改善了心脏的心脏障碍。可以将新的纳米粒子递送技术用于针对中枢神经系统的靶向治疗，以治疗以交感神经兴趣为特征的疾病。这次美国生理学会（APS）会议将重点关注许多此类机制。会议将包括自分泌，旁分泌和内分泌介质的反射和中枢神经系统区域的作用，这些区域已知可以调节交感神经功能（例如下丘脑和髓质）。研讨会和海报演示将集中于反应性氧化剂应激，一氧化氮，血管紧张素II，Angiotensn（1-7），谷氨酸，GABA，GABA以及许多这些介体的受体的转录和翻译调节。在本次会议上要讨论的研究领域对于主要自主疾病的治疗和管理以及从心血管和/或代谢性疾病演变的人的转化方法至关重要。人，动物，细胞和分子生理的融合将促进对这一生物医学领域的其他综合方法的讨论。考虑到以上，提议的会议的具体目标是：1。将自主神经性心血管生理学和病理生理学领域的领导者汇集在一起​​，以对各种疾病状态中与交感神经相关的当前研究和治疗进行激烈的讨论。 2。为初级调查人员，研究生和博士后研究员提供一个场所，以口头和海报演示的形式强调他们的研究。 3。促进针对将基础科学转化为临床疗法的新想法的产生。 4。在心血管功能的自主性调节领域之间建立新的关系。 5。提供一个国际论坛，在该论坛中，代表性不足的少数民族可以参加。公共卫生相关性：本次会议的目的是提供一个科学论坛，以交换思想，并介绍有关健康和疾病中交感神经活动的最新数据。同情激活虽然被认为是动脉压，血流和血管抗性的生理相关和重要的调节剂，但被认为是导致病理学的促进，即使过度活跃。在那些条件下尤其如此 需要高水平的交感神经来补偿异常心输出量或交感神经活动在明显不利于器官功能的范围内维持动脉压。至关重要的是，要进行异常交感神经功能的综合机制的全面理解，以便可以开发出对这些疾病的更多理性疗法。在本次会议上，我们将专门针对被认为涉及异常的疾病。这次会议将采用一种综合方法来理解交感神经调节，并将遗传，分子，细胞和整个动物方法纳入本次会议所涵盖的主题。从来没有关于此主题的APS会议。该计划将结合几个与交感神经激活有关的主题。这些将包括与中枢自分泌，旁分泌和内分泌影响有关的研讨会。将涵盖有关ACE-ACE2平衡和中央细胞信号通路的新数据。现在，氧化应激被认为是正常细胞信号传导的一部分，并且过多地有助于激活可激发细胞并有助于病理学。至少有1个研讨会和几次演讲将致力于人类的同情调节。这些谈话将包括心力衰竭，高血压，盆，恐慌症和肥胖/代谢综合征。