Stress Related Mechanisms of Hypertension Risk in Youth

描述(由申请人提供)： 这项计划项目续签申请是一项综合的多学科计划，包括四个密切相关的项目，研究压力、生活方式行为和遗传倾向在高血压临床前措施发展中的作用。新的更新应用将是将肥胖症作为中介因素纳入我们的基因/环境相互作用模型。将研究四条血管活性通路，它们可能将应激期间钠调节受损和对应激反应过度的心血管反应与高血压临床前措施的发展联系起来。 这些通路是交感神经系统、肾素-血管紧张素-醛固酮系统、内皮系统和下丘脑-垂体-肾上腺轴。具体地说，项目1和4将侧重于肾素-血管紧张素-醛固酮系统在人类和动物应激诱导的盐敏感型高血压模型中的作用。项目2(人类)和项目3(动物)将继续评估血压高反应性。项目2将继续在一组有高血压家族史的受试者中对这一模型进行评估，这些受试者将被连续评估22年。此外，这项应用的新功能将是评估下丘脑-垂体-肾上腺轴。项目3将使用空气喷射应激对Dahl盐敏感的大鼠进行检测，以检测内皮素和氧化应激的急性变化。所有四个项目都将研究肥胖增加的潜在中介作用。此外，这四个项目中的每个项目都将得到行政(核心A)、生物分析(核心B)、生物医学(核心C)以及数据管理和统计(核心D)核心的支持。

DESCRIPTION (provided by applicant): This program project renewal application is an integrated multidisciplinary program including four closely related projects examining the roles of stress, lifestyle behaviors and genetic predisposition in the development of preclinical measures of essential hypertension. New to the renewal application will be the incorporation of adiposity as a mediating factor into our gene/environment interaction model. Four vasoactive pathways will be examined which may link impaired sodium regulation during stress and exaggerated cardiovascular reactivity to stress to the development of preclinical measures of hypertension. These pathways are the sympathetic nervous system, the renin-angiotensin-aldosterone system, the endothelial system, and the hypothalamic-pituitary-adrenal axis. Specifically, Projects 1 and 4 will focus on the role of the renin-angiotensin-aldosterone system in human and animal models of stress-induced salt sensitive hypertension. Projects 2 (human) and 3 (animal) will continue in the evaluation of blood pressure hyper-reactivity. Project 2 will continue to evaluate this model in a cohort of subjects with a family history of hypertension that will have been continuously evaluated for 22 years. Also, new to this application will be evaluation of the hypothalamic-pituitary-adrenal axis. Project 3 will use air jet stress in Dahl salt-sensitive rats to examine acute changes in endothelin and oxidative stress. All four projects will examine a potential mediating role of increased adiposity. In addition, each of these four projects will be supported by an Administrative (Core A), Bioassay (Core B), Biomedical (Core C), and Data Management and Statistics (Core D) cores.