The goals and specific aims of the project remain the same as in the original application except for changes suggested by the study section (deletion of the measurement of forearm blood flow and catecholamines as well as the drug studies in years 4 & 5). The long term goal of the principal investigator is to determine the role of genetic and environmental factors in hypertension in blacks. This research will use the power of the study of twins to investigate the effect of behaviorally-induced arousal of the sympathetic nervous system (SNS) on the renal handling of sodium (Na+) and the hemodynamic and humoral factors mediating changes in Na+ excretion (ENa+).
The specific aims are to answer the following questions in man: 1.) Does behavioral induced arousal of the SNS change the renal handling of Na+? 2.) if so, what changes in hemodynamic and hormonal modulators of renal Na+ handling are correlated with these alterations? 3.) Do blacks and whites differ in ENa+ changes induced by arousal and, if so, are the correlations different? 4.) Are the associated SNS and hormonal mechanisms associated with changes in ENa+ responsible for the changes in Na+ handling both during and following the arousal period? 5.) What is the relative role of genetic and environmental factors on the response patterns? We will study a total of 100 male twin pairs (50 will be black, 50 will be white). There will be equal numbers of monozygotic and dizygotic twins. The protocol we have developed induces SNS arousal by challenging pairs of subjects to compete with each other for one hour using computer based tasks. During this protocol we will measure blood pressure and heart rate, renal plasma flow (PAH), glomerular filtration rate (creatinine or inulin), proximal Na+ reabsorption (lithium clearance), total ENa+, plasma renin activity, aldosterone and cortisol to evaluate how SNS arousal reduces Na+ excretion and changes systemic and renal hemodynamics before, during and after SNS arousal. Data analyses using uni- and multivariate techniques will be used to answer the questions posed.
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