Neural Processing in the Lamina Terminalis in Long-Term Regulation of Blood Press

血压长期调节中终板的神经处理

• 批准号: 8376388
• 负责人: ALAN Kim JOHNSON
• 金额: $ 33.87万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8376388
• 关键词: Acetylcholine; Acute; Address; Affect; Aldosterone; Amygdaloid structure; Angiotensin II; Angiotensins; Animals; Area; Behavior; Behavior Control; Biological Neural Networks; Blood; Blood Circulation; Blood Pressure; Body Fluids; Brain; Brain region; Calcium; Cardiovascular Physiology; Cardiovascular system; Cations; Cell Nucleus; Cells; Chronic; Development; Disease; Equilibrium; Etiology; Fluid Balance; Functional disorder; Generations; Heart Rate; Heart failure; Homeostasis; Hormonal; Hypertension; Hypotension; Hypothalamic structure; Image; In Vitro; Investigation; Knowledge; Laboratories; Lamina Terminalis; Lesion; Life; Liquid substance; Measurement; Medial; Mediation; Mineralocorticoid Receptor; Mineralocorticoids; Molecular and Cellular Biology; NADPH Oxidase; Neuraxis; Neurobiology; Neurons; Osmolar Concentration; Output; Physiological; Process; Program Research Project Grants; Prosencephalon; Proteins; Protocols documentation; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Reflex action; Regulation; Renin-Angiotensin System; Research; Resources; Role; Saline; Signal Transduction; Signaling Molecule; Slice; Structure; Superoxide Dismutase; System; Techniques; Testing; Third ventricle structure; Tissues; Vanilloid; Work; basal forebrain; blood pressure regulation; copper zinc superoxide dismutase; extracellular; in vivo; indexing; information processing; neural information processing; paraventricular nucleus; receptor; receptor expression; relating to nervous system; research study

The central nervous system coordinates effector systems that control blood pressure. Structures of the lamina terminalis (LT) receive and process information about of the status of the cardiovascular system and body fluid balance. Processed output from the LT is projected into a neural network that regulates blood pressure over the long term. Therefore the LT is a pivotal neural node for determining cardiovascular homeostasis. In recent studies, we have discovered that antagonism of brain mineralocorticoid receptors (MR), angiotensin Type 1 receptors (ATrR), or transient receptor potential, vanilloid Type 1 (TRPV1) channel or increased scavenging of central reactive oxygen species (ROS) block the development of mineralocorticoid (MC)-induced hypertension (HT). The primary hypothesis to be tested in this proposal is that neurons in structures of the LT use MR, AT^R, ROS, and TRPV1 channels in information processing that is essential for maintaining normal blood pressure and body fluid homeostasis. To test this hypothesis, both in vivo and in vitro experiments will be conducted in which MR, ATrR, ROS, and TRPV1 proteins are manipulated within structures of the LT. The experiments will address the following four specific aims: Aim 1. determine if components of the LT are critical for the roles of MR, AT^R, ROS and TRPV1 channels in aldosterone (ALDO)-induced HT; Aim 2. determine the effects of ALDO pretreatment on angiotensin II (ANG II), hypertonic saline (HTS) or acetylcholine (ACh) activation of cells in the LT; Aim 3. determine the effects of ALDO pretreatment on ROS generation and on ANG IIinduced release of intracellular ROS ([ROS]() in the LT; and Aim 4. determine the effects of ALDO pretreatment on expression of ATrR, superoxide dismutase (SOD) and NADPH oxidase in the LT. Techniques to be applied include chronic telemetric measurements of blood pressure and heart rate, in vitro imaging in living brain slices to determine induced changes in intracellular calcium ([Ca2+]j) and [ROS]j, and quantitative determination of the expression of key signaling molecules that have been implicated in MC-induced HT. New knowledge derived from studies on the mechanisms of LT neuronal function in reception and processing of information is highly relevant to understanding the pathophysiology associated with disordered fluid and cardiovascular regulation. This new information will be critical for a fuller understanding of the etiology and treatment of diseases such as hypertension and heart failure.

中枢神经系统协调控制血压的效应系统。结构 Lamina Terminalis（LT）接收和处理心血管状态的信息 系统和体液平衡。从LT的处理输出投影到一个神经网络中 长期调节血压。因此，LT是确定的关键神经节点 心血管稳态。在最近的研究中，我们发现大脑的拮抗作用 盐皮质激素受体（MR），血管紧张素1型受体（ATRR）或瞬态受体电位， Vanilloid 1型（TRPV1）通道或中央活性氧（ROS）的清除量增加 阻止矿物皮质激素（MC）诱导的高血压（HT）的发展。主要假设 在此提案中进行测试的是，LT结构中的神经元MR，AT^R，ROS和 信息处理中的TRPV1通道对于维持正常血液至关重要 压力和体液稳态。为了检验该假设，体内和体外实验均 将进行MR，ATRR，ROS和TRPV1蛋白在结构中操纵 上尉。实验将解决以下四个特定目标：目标1。确定是否是否 LT的组件对于MR，AT^r，ros和Trpv1通道的角色至关重要 醛固酮（Aldo）引起的HT；目标2。确定Aldo预处理对 血管紧张素II（ANG II），高渗盐水（HTS）或乙酰胆碱（ACH）在细胞中的活化 lt;目标3。确定Aldo预处理对ROS生成和ANG II诱导的影响 释放细胞内ROS（[ROS]（）在LT中； AIM 4。确定Aldo的影响 对ATRR表达，超氧化物歧化酶（SOD）和NADPH氧化酶的表达预处理 上尉要应用的技术包括血压和心脏的慢性远程测量 速率，在活脑切片中的体外成像以确定诱导的细胞内钙的变化（[Ca2+] J） [ROS] J，以及定量确定已经是关键信号分子的表达 与MC诱导的HT有关。从有关LT神经元机制的研究得出的新知识 在接收和处理信息中的功能与理解 与液体无序和心血管调节有关的病理生理学。这个新信息 对诸如高血压等疾病的病因和治疗更充分的了解至关重要 和心力衰竭。