In rats and mice, fasting suppresses and sucrose overfeeding stimulates sympathetic nervous system (SNS) activity. Fasting hypoglycemia in rats suppresses SNS activity while stimulating adrenal medullary catecholamine release. Administration of 2-deoxy-D-glucose (2-DG), an inhibitor of intracellular glucose metabolism, also stimulates the adrenal medulla. The studies reported here were undertaken to determine the SNS response to chronic 2-DG administration and to test the hypothesis that diet-induced changes in SNS activity are related to central nervous system glucose metabolism. Ingestion of 2-DG caused an increase in urinary epinephrine excretion and significant depletion of adrenal epinephrine content, both indices of adrenal medullary stimulation. Chronic sc injections of 2-DG in animals with normal or increased food consumption caused simultaneous suppression of cardiac sympathetic nerve activity, as evidenced by diminished cardiac [3H]norepinephrine turnover, and stimulation of adrenal medullary epinephrine release. Parenteral 2-DG administration to adrenalectomized rats also caused suppression of cardiac sympathetic activity. Thus, this response to neuroglycopenia is independent of adrenal medullary catecholamine release. These results indicate that central nervous system glucose metabolism may mediate diet-induced changes in SNS activity.
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