Stress Related Mechanisms of Hypertension Risk

描述(由申请人提供)： 本计划项目申请由多学科综合组成 计划包括4个密切相关的项目，研究压力的作用， 生活方式行为和遗传多态性在儿童精神分裂症发生发展中的作用 高血压(EH)的临床前措施。该计划项目是 由4核支持。将检查三条血管活性通路，它们可能 心血管(CV)反应性夸大与心血管恢复延迟有关 重视EH临床前治疗措施的发展。这些路径是 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涉及继续评价 有17年以上EH家族病史的青年。 项目1将侧重于环境压力的作用(例如，较低 社会经济地位、较高的个人生活压力)与4 3条血管活性通路(RAAS、SNS、ES)的基因多态性 CV对急性实验室挑战的反应性和临床前研究进展 疾病测量(例如，左心室重量增加、静息时间增加 血压升高，微量白蛋白升高，内皮功能下降 和动脉僵硬增加)。项目2将研究可能的种族 延迟的BP恢复对于延长的实验室挑战的差异 主要是由于RAAS系统的失调和无效的钠 正在处理。这些参数之间的关系，关联的3个多态 使用SNS和RAAS以及临床前疾病措施也将进行评估。 项目3将考察运动训练对非裔美国人的影响 儿童对急性实验室挑战和临床前的BP反应 通过改善ES来衡量疾病。将进行项目4 并将评估间歇性应激的影响 高盐饮食对血管和肾脏发育的影响机制 嗯。它被设计用来识别与血管和血管相关的新候选基因 与应激暴露相关的肾功能障碍。这四个项目将 每一项都由生物分析(核心B)、生物医学(核心C)和数据管理提供支持 和统计(核心D)核心。

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.