Stress Related Mechanisms of Hypertension Risk in Youth

描述（由申请人提供）： 该计划项目更新申请是一个综合的多学科计划，包括四个密切相关的项目，研究压力，生活方式行为和遗传易感性在原发性高血压临床前措施的发展中的作用。新的更新应用将是将肥胖作为一个中介因素纳入我们的基因/环境相互作用模型。将检查四种血管活性通路，其可能将应激期间受损的钠调节和对应激的过度心血管反应性与高血压临床前指标的发展联系起来。 这些途径是交感神经系统、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。具体而言，项目1和4将集中在应激诱导的盐敏感性高血压的人类和动物模型中的作用，肾素-血管紧张素-醛固酮系统。项目2（人）和项目3（动物）将继续评价血压高反应性。项目2将继续在一组有高血压家族史的受试者中评价该模型，该受试者将被连续评价22年。此外，新的应用将是下丘脑-垂体-肾上腺轴的评价。项目3将在达尔盐敏感大鼠中使用空气喷射应激来检查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，这四个项目中的每一个都将得到行政（核心A）、生物测定（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.