SELECTIVE CONTROL OF RELEASE FROM CHROMAFFIN CELLS

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The overall purpose of the proposed research is to gain a greater understanding of the role of the adrenal medulla in cardiovascular regulation. Experiments will be conducted in male Sprague-Dawley rats to test the hypothesis that: the ratios of norepinephrine (NE) and epinephrine (EPI) released from the adrenal gland vary depending upon the homeostatic challenge. Moreover, the proportions of catecholamines released contribute significantly to the production of appropriate hemodynamic adjustments. Three physiologic challenges: hypoglycemia, hypotension and cold exposure were selected for study because they evoke a diverse range of cardiovascular adaptations. Moreover, in preliminary studies they differentially affected adrenal medullary catecholamine release; hypoglycemia preferentially elicited release from EPI cells, whereas hypotension and cold exposure stimulated NE cells. The specific aims of the project are: 1.) To demonstrate that EPI and NE cells may be preferentially stimulated. Neurally mediated activation of the adrenal will be elicited with the three physiologic challenges and the ratios of EPI to NE released will be measured by the technique of in vivo medullary dialysis 2.) To assess the impact that different proportions of catecholamine released from the adrenal have on the hemodynamic adjustments to hypoglycemia, hypotension and cold exposure. Hemodynamic parameters to be assessed are blood pressure, cardiac output, resistances and blood flow distributions to vascular beds (using Doppler flow probes and radiolabeled microspheres). These experiments will be conducted in conscious animals with three levels of sympathetic function: neurons destroyed (adrenal medulla intact), adrenal demedullated (neurons intact) and normal animals (adrenal medulla and neurons intact). 3.) To assess the possibility that angiotensin II may act as modulator of neurally mediated catecholamine release and thereby influence the ratios of EPI and NE released. The effects of angiotensin II on the quantity and ratios of EPI and NE released from the adrenal medulla in response to stimulation of the preganglionic innervation will be assessed. Thus, the proposed project should provide significant new evidence that mechanisms exist for chromaffin cells to be selectively controlled, and thereby, provide a greater understanding of the diversity of adrenal medullary contributions to cardiovascular regulation.