Impaired Sodium Regulation and BP in Obese Youth

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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.