Impaired Sodium Regulation and BP in Obese Youth

描述（由申请人提供）：背景：肥胖现在被认为是美国头号健康问题。肥胖及其后果在儿童中尤其令人不安，在过去二十年中，儿童的肥胖患病率翻了一番。高血压以及与心脏、肾脏和脉管系统相关的血压变化是儿童期肥胖的主要后果。这些变化背后的机制尚未确立。目的：本研究的目的是验证应激诱导的压力性尿钠受损通过增加个体因应激而暴露于心血管负荷而导致肥胖个体发生原发性高血压及其后遗症的假设。方法：选取年龄在15-18岁之间的80名肥胖和80名非肥胖受试者，采用标准的5小时方案，分两次进行测试。他们会在第三个小时玩一系列的视频游戏。目的：本研究的目的是验证以下假设：(1)肥胖和非肥胖青少年在控制期条件下与在压力期条件下观察到的动态血流动力学反应模式存在差异；(2)肥胖青少年与非肥胖青少年在控制期与应激期的动态尿内分泌反应模式存在差异；(3)应激状态下的反应模式与肥胖个体靶器官心脏和肾脏的变化有关。肥胖的测量将通过测量体脂百分比的双能x射线吸收仪和测量内脏脂肪组织的磁共振成像来确定。内分泌功能的测量将包括肾素-血管紧张素-醛固酮系统和交感神经系统的活动。脂肪组织衍生物质的影响也将被检查，包括瘦素和血管紧张素原。最后，靶器官变化的测量将包括左心室质量、舒张功能和肾小球高滤过（由肌酐清除率估计）。

DESCRIPTION (provided by applicant): Background: Obesity is now considered the number one health concern in the United States. Obesity and its consequences are particularly disturbing in children in whom the prevalence of obesity has doubled over the last two decades. Hypertension and associated blood pressure-related changes to the heart, kidney, and vasculature are major consequences of obesity in childhood. The mechanisms underlying these changes have yet to be established. Purpose: The purpose of the proposed study is to test the hypothesis that stress-induced impaired pressure natriuresis contributes to the development of essential hypertension and its sequelae in obese individuals by increasing the cardiovascular load the individual is exposed to as a result of the stress. Methods: A total of 80 obese and 80 nonobese subjects aged 15-18 years will be tested using a standard 5 hour protocol on two occasions. They will play a series of video games during hour three on one occasion. Aims: The aims of the proposed study are to test the following hypotheses: (1) obese and nonobese adolescents show differences in dynamic hemodynamic response patterns observed under a control period condition compared to a condition during which the adolescent is exposed to a period of stress; (2) obese and non-obese adolescents show differences in dynamic urinary and endocrine response pattern observed under a control period condition compared to a condition during which the adolescent is exposed to a period of stress; and (3) the response pattern during the stress condition will be related to measures of target organ changes to the heart and kidney in obese individuals. Measures of obesity will be determined by dual-energy x-ray absorptiometry for the measurement of percent body fat and magnetic resonance imaging for the measurement of visceral adipose tissue. Measures of endocrine function will include the activity of the renin-angiotensin- aldosterone system and the sympathetic nervous system. The effects of adipose tissue-derived substances will also be examined, including leptin and angiotensinogen. Finally, measures of target organ change will include left ventricular mass, diastolic function, and glomerular hyperfiltration as estimated from creatinine clearance.