Impaired Sodium Regulation and BP in Obese Youth

描述(申请人提供)：背景：肥胖现在被认为是美国的头号健康问题。肥胖及其后果在儿童中尤其令人不安，他们的肥胖率在过去20年中翻了一番。高血压和与血压相关的心脏、肾脏和血管系统的变化是儿童肥胖的主要后果。这些变化背后的机制尚未建立。目的：本研究的目的是验证一种假说，即应激诱导的压力受损的钠尿通过增加个体因应激而暴露的心血管负荷而导致肥胖个体的高血压及其后遗症的发生。方法：总共80名15-18岁的肥胖者和80名非肥胖者将使用标准的5小时程序进行两次测试。他们将在第三个小时内一次玩一系列电子游戏。目的：本研究的目的是检验以下假设：(1)肥胖和非肥胖青少年在控制期条件下观察到的动态血流动力学反应模式与青少年暴露在应激期条件下的不同；(2)肥胖和非肥胖青少年在控制期条件下观察到的动态尿液和内分泌反应模式与青少年暴露在应激期条件下的不同；以及(3)应激条件下的反应模式将与肥胖者心脏和肾脏的靶器官变化的测量有关。肥胖的测量将通过测量身体脂肪百分比的双能X射线吸收法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。还将检查脂肪组织衍生物质的影响，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重量、舒张期功能和肾小球高滤过，从肌酐清除量估计。

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.