The research will investigate mechanisms responsible for peripheral vasodilation. Our hypotheses are: 1) In CHF, more than one mechanism is responsible for impaired vasodilation, one is related to salt and water retension. The second is postulated to be due to detraining; 2) training leads to enhanced vasodilation that is mediated by structural changes (independent of metabolic differences). This enhanced vasodilation is related in part to training induced changes in vessel size. These changes in size may be mediated by the release of endothelial substances; 3) training leads to changes in somatic afferent stimulation that are due to differences in local metabolism. Thus, training induced changes in metabolism can affect blood flow in uninvolved vascular beds but these changes in metabolism do not effect local vasodilation; 4) the sympathetic nervous system plays an integral role in increasing resistance in metabolically active areas in distant areas. This system may be modulated by training. This revised proposal uses a number of models to address these questions. 1) Human peripheral vasodilation is studied in response to ischemia and forearm work. Blood flow is measured noninvasively with strain gauge plethysmography. 2) Human large blood vessel diameter is measured by combined plethysmography and brachial artery velocity measurements (area=flow/velocity). 3) Indices of peripheral metabolism are studied using 31P NMR spectroscopy. 4) Somatic afferent nerve stimulation will be studied by using microneurographic techniques to investigate the efferent response to afferent stimulation. 5) This intrinsic dilatory characteristics of blood vessels will be studied using rat aorta rings and segments. The studies proposed will be part of the candidate's training program designed to improve his skills and understanding of 1) human blood flow; 2) muscle metabolism; 3) the sympathetic nervous system in human beings (using microneurography); and 4) basic mechanisms of vasodilation in an animal model. A newly refurbished laboratory, equipped for exercise and plethysmography studies, will be at the candidate's disposal. Also, a 350 sq ft animal laboratory is available. Preliminary NMR studies are currently underway and plans to learn microneurography have been made. The Hershey Medical Center is supportive of these efforts.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
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Pennsylvania State University
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