CARDIOVASCULAR DYNAMICS AND THEIR CONTROL

心血管动力学及其控制

• 批准号: 7777056
• 负责人: John E Hall
• 金额: $ 6.25万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7777056
• 关键词: Acute; Androgens; Animal Experiments; Animal Model; Animals; Area; Baroreflex; Biochemical; Biochemistry; Biomedical Engineering; Blood Circulation; Blood Vessels; Body Fluids; CYP4A2 gene; Canis familiaris; Cardiovascular Diseases; Cardiovascular system; Chemical Engineering; Chronic; Clinical Medicine; Complex; Computers; Development; Discipline; Disease; Electrical Engineering; Endocrine system; Endocrinology; Endothelin; Etiology; Excretory function; Feedback; Functional disorder; Genetic; Genetic Engineering; Genetic Models; Goals; Heart failure; Histological Techniques; Histology; Hormonal; Human; Hypertension; Image; Kidney; Longitudinal Studies; Mathematics; Measures; Mediating; Medicine; Methods; Molecular; Molecular Biology; Molecular Genetics; Mus; Natriuresis; Nature; Nerve; Neuraxis; Neurobiology; Obesity; Pathology; Perfusion; Physiological; Physiology; Placenta; Play; Postmenopause; Process; Rattus; Regulation; Research; Research Personnel; Rodent; Role; Services; Signal Pathway; Sodium; Sympathetic Nervous System; System; Systems Analysis; Techniques; Technology; Testing; Time; Training; Training Programs; Translations; abstracting; blood pressure regulation; imaging modality; instrument; instrumentation; interdisciplinary approach; interest; member; neuromechanism; novel; pregnant; pressure; programs; release factor; research study; theories; tool

DESCRIPTION (provided by applicant): This program, which began more than 39 years ago, brings together investigators from multiple disciplines with an interest in the integrative control of circulatory function. Our major long-term goal has been to develop a quantitative analysis of cardiovascular (CV) dynamics and related control systems, including the kidneys, sympathetic nervous system (SNS), and endocrine systems. Two unique features of this program are: 1) it utilizes an integrative approach to understand complex interactions between multiple components of CV control systems, and 2) it focuses mainly on long-term control of the circulation because many CV diseases, such as hypertension, are manifestations of abnormal control mechanisms that develop slowly over long periods of time. The research proposed in this application is described by the titles of the projects as follows: I. Neurohumoral and Renal Mechanisms of Hypertension; this project will elucidate the neurohumoral mechanisms, central nervous system (CMS) circuits and signaling pathways that mediate obesity induced SNS activation, impaired renal-pressure natriuresis and hypertension. II. Renal Control of Body Fluid Volumes and Circulatory Dynamics; this project will determine the role of factors released by the placenta in causing endothelial dysfunction, impaired renal-pressure natriuresis and hypertension during chronic reductions in uterine perfusion pressure in pregnant rats. III. (previously Project V) Hormonal Mechanisms of Postmenopausal Hypertension; this project will test the hypothesis that post-menopausal hypertension is mediated by increases in 20-HETE and/or increases in preglomerular vascular sensitivity to 20-HETE and that androgens increase 20-HETE by increasing expression of CYP4A2 and by increasing intrarenal Ang II and endothelin. IV. Neural Mechanisms in Cardiorenal Regulation; this project will use sophisticated techniques in chronically instrumented dogs to determine whether the CMS plays an important role in chronic resetting of the baroreflex and whether chronic activation of the baroreflex has sustained effects to inhibit renal sympathetic nerve activity, promote sodium excretion and reduce arterial pressure. The total program, including core support services, provides a unique interdisciplinary approach toward developing an integrative analysis of long-term regulation of blood pressure and circulatory dynamics in several forms of experimental hypertension that have great relevance to human hypertension. (End of Abstract)

描述（由申请人提供）： 该计划始于39年前，它汇集了来自多个学科的研究人员，对循环功能的综合控制感兴趣。我们的主要长期目标是对心血管（CV）动力学和相关控制系统（包括肾脏，交感神经系统（SNS）和内分泌系统）进行定量分析。该程序的两个独特功能是：1）它利用一种集成方法来理解CV控制系统多个组件之间的复杂相互作用，2）它主要集中于对循环系统的长期控制，因为许多CV疾病（例如高血压）都是异常控制机制的表现，这些机制在长时间的时间内会缓慢发展。该应用程序中提出的研究用如下的项目描述：I。高血压的神经肿瘤和肾脏机制；该项目将阐明介导肥胖感引起的SNS激活，肾压纳特里氏菌和高血压受损的神经肿瘤机制，中枢神经系统（CMS）电路（CMS）电路和信号通路。 ii。体液体积和循环动力学的肾脏控制；该项目将确定胎盘释放的因素在引起内皮功能障碍，肾脏压力纳地尿症的受损和高血压期间的慢性降低子宫灌注压力中的高血压。 iii。 （以前的项目V）绝经后高血压的激素机制；该项目将检验以下假设：绝经后高血压是由20-HETE的增加和/或增加不能骨前血管对20-HETE的敏感性的介导的，并且通过增加CYP4A2的表达和增加植物内元ANG II和内皮素，雄激素增加了20-HETE。 iv。心脏调节中的神经机制；该项目将在长期仪器的狗中使用复杂的技术来确定CMS在慢性重置降压力反射中是否起重要作用，以及降压体的慢性激活是否具有持续的影响，可抑制肾交感神经活性，促进钠排泄物，促进钠排泄量并降低动脉压力。包括核心支持服务在内的总计划提供了一种独特的跨学科方法，以对几种与人类高血压具有很大相关的几种实验性高血压的长期调节进行整合分析。 （抽象的结尾）