Stress Related Mechanisms of Hypertension Risk

高血压风险的压力相关机制

• 批准号: 7091670
• 负责人: GREGORY ALAN HARSHFIELD
• 金额: $ 205.28万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7091670
• 关键词: clinical research; environmental stressor; essential hypertension

DESCRIPTION (provided by applicant): This program project application consists of an integrated multidisciplinary program including 4 closely related projects examining the roles of stress, lifestyle behaviors and genetic polymorphisms in the development of preclinical measures of essential hypertension (EH). The Program Project is supported by 4 cores. Three vasoactive pathways will be examined which may link exaggerated cardiovascular (CV) reactivity and delayed CV recovery from stress to development of preclinical measures of EH. These pathways are Sympathetic Nervous System (SNS), Renin-Angiotensin-Aldosterone System (RAAS) and Endothelial System (ES). Project 1 involves the continued evaluation of youth with family histories of EH over a cumulative period of 17 years. Project 1 will focus upon the role of environmental stress (e.g., lower socioeconomic status, high personal life stress) in combination with 4 polymorphisms associated with the 3 vasoactive pathways (RAAS, SNS, ES) upon CV reactivity to acute laboratory challenges and development of preclinical measures of disease (e.g., increased left ventricular mass, increased resting blood pressure (BP), increased micro albumin, decreased endothelial function and increased arterial stiffness). Project 2 will examine possible ethnic differences in delayed BP recovery to an extended laboratory challenge primarily due to dysregulation of the RAAS system and ineffective sodium handling. Relationships between these parameters, 3 polymorphisms associated with SNS and RAAS and preclinical measures of disease will also be evaluated. Project 3 will examine impact of exercise training in African American children on BP reactivity to an acute laboratory challenge and preclinical measures of disease via improvements in the ES. Project 4 will be conducted on Dahl salt-sensitive rats and will assess the impact of intermittent stress and high salt diet upon vascular and renal mechanisms in the development of EH. It is designed to identify new candidate genes related to vascular and renal dysfunction associated with stress exposure. These four projects will each be supported by Bioassay (Core B), Biomedical (Core C) and Data Management and Statistics (Core D) cores.

描述（由申请人提供）： 该计划项目应用程序由一个综合的多学科组成 计划包括4个密切相关的项目，检查压力的作用， 生活方式行为和遗传多态性在发展中 基本高血压（EH）的临床前度量。程序项目是 由4个内核支撑。将检查三个血管活性途径 链接夸张的心血管（CV）反应性和从延迟的CV恢复 压力EH的临床前度量。这些途径是 交感神经系统（SNS），肾素 - 血管紧张素 - 醛固酮系统（RAAS） 和内皮系统（ES）。项目1涉及对 在17年的累积期间，具有EH家庭历史的年轻人。 项目1将侧重于环境压力的作用（例如，较低 社会经济地位，高个人生活压力）与4结合 与3个血管活性途径（RAAS，SNS，ES）相关的多态性 简历对急性实验室挑战的反应性和临床前的发展 疾病的度量（例如，左心室质量增加，静止增加 血压（BP），微白蛋白增加，内皮功能降低 并增加了动脉刚度）。项目2将检查可能的种族 BP恢复延迟到扩展实验室挑战的差异 主要是由于RAAS系统的失调和无效的钠 处理。这些参数之间的关系，与3个相关的多态性 还将评估使用SNS和RAAS以及临床前疾病措施。 项目3将检查非裔美国人运动训练的影响 BP对急性实验室挑战和临床前的反应性儿童 通过改善ES的疾病度量。项目4将进行 关于达尔盐敏感大鼠，将评估间歇性压力的影响 以及在发育中的血管和肾脏机制上的高盐饮食 嗯。它旨在识别与血管和血管相关的新候选基因 与压力暴露有关的肾功能障碍。这四个项目将 每个人都得到生物测定（核心B），生物医学（核心C）和数据管理的支持 和统计（核心D）内核。