Research Profile: Our investigational clinical interests involve the regulation of heart rate and blood pressure in children and adolescents. Circulatory physiology remains ill-determined in children with a variety of problems with neurovascular dysfunction. We have established a Center for Hypotension-Related Disease aimed at young people from childhood through young adult with neurally mediated syncope, chronic orthostatic intolerance, chronic fatigue syndrome, orthostatic intolerance of other etiologies such as occur in the postural tachycardia syndrome (POTS). Research focus is on circulatory and vascular problems and their autonomic consequences including altered peripheral arterial and venous properties and changes in blood volume and its redistribution. Molecular mechanisms including cytokine and nitric oxide assessment are explored. Treatment protocols are tested. Methods include plethysmographic measurements of peripheral and central blood flow, capacitance and peripheral permeability measurements, skin blood flow measurements using laser-Doppler flowmetry, baroreflex assessment, standard circulatory autonomic function tests, assessment of the efficacy of the skeletal muscle pump, and tests of heart rate and blood pressure variability. Orthostatic stress is used as a provocative stimulus. Other research interests include computational circulatory physiology investigating vascular and cardiac properties in animal model systems as well as during diagnostic procedures such as cardiac catheterization and flow-volume monitoring and redistribution in critically ill infants and children. Correlative work studying the relation of cardiovascular properties to nitric oxide physiology is in progress. Recent work has also included connections of peripheral flow and muscle pump activity with osteoporosis, and contractual work with the Department of Defense related to muscular dystrophy.