Central Renin-Angiotensin System: Metabolism, Fluid Balance, and Hypertension

中央肾素-血管紧张素系统：代谢、体液平衡和高血压

• 批准号: 7770209
• 负责人: Justin L Grobe
• 金额: $ 10.56万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7770209
• 关键词: Adult; Area; Basal metabolic rate; Blood Pressure; Blood Vessels; Brain; Cardiac; Cardiovascular Diseases; Cardiovascular Physiology; Consummatory Behavior; Development; Disease; Economics; Equilibrium; Fluid Balance; Genes; Genetic Recombination; Health; Hormones; Hypertension; Institution; Journals; Kidney; Laboratories; Laboratory Research; Learning; Liquid substance; Mediating; Mental Depression; Mentors; Metabolic; Metabolism; Microinjections; Modeling; Mus; Neuraxis; Obesity; Peripheral; Phase; Phenotype; Population; Preparation; Principal Investigator; Productivity; RNA; Regulation; Renin-Angiotensin System; Research; Resources; Sampling; Signal Pathway; Sodium; Structure; System; Techniques; Tissues; Training; Transgenic Mice; United States; Viral; Virus; editorial; hypertensive heart disease; mouse model; programs; psychologic; public health relevance; social

DESCRIPTION (provided by applicant): Program Director/Principal Investigator (Last, First, Middle): GROBE, JUSTIN L. Project Summary Metabolic and cardiovascular disorders both pose significant threats to the health of the adult population of the United States and world-wide. Both types of disorders are present in at least 33% of the population, and the economic, social, psychological, and productivity burdens which result from these disorders are estimated to be in excess of $530 billion. One hormone system involved in the regulation of both metabolism and cardiovascular function is the Renin- Angiotensin System (RAS). While the RAS is found in many tissues throughout the body, the Sigmund laboratory has previously developed a transgenic mouse model (the sRA model) in which overactivity of the RAS is limited to the central nervous system. Brain-specific overactivity of the RAS in these mice results in moderate hypertension and cardiac remodeling, a large increase in basal metabolic rate, sustained depression of body mass, and decreased adiposity. The current proposal will evaluate the angiotensinergic signaling pathways within the brain which induce these phenotypes (during the mentored phase), and then examine the efferent, peripheral mechanisms which mediate these phenotypes (upon the establishment of an independent research laboratory). Specifically, during the mentored phase, the candidate will learn techniques related to the microinjection delivery of viruses which induce gene recombination within select brain structures (viral preparation/use, electrophoretic microinjection, immunohistology, small-sample RNA preparation, quantitative PCR). Additionally, during the mentored phase, the candidate will continue his professional development (mentoring of junior colleagues, further expansion of intellectual and collaborative resources, and the unique proximity to the editorial office of a major area-specific scientific journal). Collectively, this project will facilitate continued technical, intellectual, and professional training for the candidate, and assist in the establishment of an independent research laboratory at an academic research institution. PHS 398/2590 (Rev. 11/07) Continuation Format Page PUBLIC HEALTH RELEVANCE: Program Director/Principal Investigator (Last, First, Middle): GROBE, JUSTIN L. Relevance The Renin-Angiotensin System (RAS) is a hormone system involved in the regulation of renal, cardiac, and vascular structure and function, fluid and sodium consummatory behavior, blood pressure, and metabolic rate. In the current proposal, transgenic mice with brain-specific overactivity of the RAS are utilized to evaluate the mechanisms by which the brain's RAS regulates metabolism and hydromineral balance. PHS 398/2590 (Rev. 11/07) Continuation Format Page

描述（由申请人提供）： 计划主管/首席研究员（最后，第一，中间）：Grobe，Justin L.项目摘要代谢和心血管疾病都对美国和全球成年人口的健康构成了重大威胁。两种类型的疾病至少存在于33％的人口中，据估计，这些疾病导致的经济，社会，心理和生产力负担超过5,300亿美元。 肾素 - 血管紧张素系统（RAS）涉及一种激素系统。尽管在整个身体的许多组织中都发现了RAS，但Sigmund实验室以前已经开发了一种转基因小鼠模型（SRA模型），其中RAS的过度活动仅限于中枢神经系统。这些小鼠中RA的大脑特异性过度活动导致中度高血压和心脏重塑，基础代谢率大大增加，体重降低以及肥胖降低。 当前的建议将评估诱导这些表型（在指导阶段）的大脑内的血管紧张素信号传导途径，然后检查介导这些表型的传出的外围机制（建立了独立的研究实验室）。具体而言，在指导阶段，候选人将学习与诱导精选脑结构内基因重组的病毒重组有关的技术（病毒制备/使用，电泳微注射，免疫组织学，小样本RNA制备，定量PCR）。此外，在指导阶段，候选人将继续他的专业发展（对初级同事的指导，智力和协作资源的进一步扩展以及与主要领域特定科学杂志的社论办公室的独特接近）。总的来说，该项目将促进候选人的持续技术，智力和专业培训，并协助在学术研究机构建立独立的研究实验室。 PHS 398/2590（Rev. 11/07）延续格式页面 公共卫生相关性： 计划主管/首席研究员（最后，第一，中间）：Grobe，Justin L.肾素 - 血管紧张素系统（RAS）是一种激素系统，涉及肾脏，心脏和血管结构和血管结构和功能，流体和钠的完整性行为，血压和新代谢率。在当前的建议中，利用具有大脑特异性过度活动的转基因小鼠评估大脑RAS调节代谢和氢化层平衡的机制。 PHS 398/2590（Rev. 11/07）延续格式页面