The long term objective of the present proposal is to characterize some of the factors that regulate the activity of the sympathetic nervous system and the adrenal medulla and thereby help define the role played by catecholamines in the regulation of metabolism and in the maintenance of the internal environment. Utilizing kinetic techniques to asses sympathetic nervous system activity by measuring the rate of norepinephrine turnover in adrenergically innervated tissues of experimental animals, the studies planned in this program will investigate the following areas: 1) The effect of different nutrients on the activity of the sympathetic nervous system, the adrenal medulla, and the peripheral dopaminergic system; 2) The metabolic signals that coordinate dietary intake with sympathoadrenal and dopaminergic activity; and 3) The sympathoadrenal and dopaminergic responses in a variety of physiological and pathophysiological states including experimental diabetes, renal insufficiency, pregnanay, hypoxia, and fever. Since the sympathetic nervous system plays a critical role in the regulation of thermogenesis and blood pressure, the studies examining the effect of dietary intake on the activity of this system may have implications for the pathogenesis and treatment of obesity and hypertension. Identification of altered sympathoadrenal and dopaminergic responses in other physiological and pathophysiological states may have therapeutic implications since effective means of stimulating or blocking the actions of catecholamines are readily available.

National Institute of Health (NIH)
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Research Project (R01)
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Metabolism Study Section (MET)
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Beth Israel Deaconess Medical Center
United States
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Johnson, T S; Rock, P B; Young, J B et al. (1988) Hemodynamic and sympathoadrenal responses to altitude in humans: effect of dexamethasone. Aviat Space Environ Med 59:208-12
Walgren, M C; Young, J B; Kaufman, L N et al. (1987) The effects of various carbohydrates on sympathetic activity in heart and interscapular brown adipose tissue of the rat. Metabolism 36:585-94
Williams, M; Young, J B; Rosa, R M et al. (1986) Effect of protein ingestion on urinary dopamine excretion. Evidence for the functional importance of renal decarboxylation of circulating 3,4-dihydroxyphenylalanine in man. J Clin Invest 78:1687-93
Landsberg, L (1986) Diet, obesity and hypertension: an hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis. Q J Med 61:1081-90
Landsberg, L; Young, J B (1986) Caloric intake and sympathetic nervous system activity. Implications for blood pressure regulation and thermogenesis. J Clin Hypertens 2:166-71
Kaufman, L N; Young, J B; Landsberg, L (1986) Effect of protein on sympathetic nervous system activity in the rat. Evidence for nutrient-specific responses. J Clin Invest 77:551-8
Young, J B; Kaufman, L N; Saville, M E et al. (1985) Increased sympathetic nervous system activity in rats fed a low-protein diet. Am J Physiol 248:R627-37
Kaplan, M M; Young, J B; Shaw, E A (1985) Abnormal thyroid hormone binding to serum proteins in ob/ob and db/db genetically obese mice. Endocrinology 117:1858-63
Landsberg, L; Young, J B (1985) Insulin-mediated glucose metabolism in the relationship between dietary intake and sympathetic nervous system activity. Int J Obes 9 Suppl 2:63-8