SELECTIVE CONTROL OF RELEASE FROM CHROMAFFIN CELLS

拟议研究的总体目的是为了获得更大的 对肾上腺髓质在心血管疾病中作用的认识 监管。实验将在雄性Spraogue-Dawley大鼠身上进行 为了检验假设：去甲肾上腺素(NE)和 肾上腺释放的肾上腺素(EPI)取决于 动态平衡挑战。此外，儿茶酚胺的比例 发布显著有助于生产适当的 血液动力学调整。三个生理挑战：低血糖， 低血压和寒冷暴露被选为研究对象，因为它们能唤起 各种各样的心血管适应能力。此外，在初赛中， 它们对肾上腺髓质儿茶酚胺有不同影响的研究 释放；低血糖优先引起外周血细胞释放， 而低血压和冷暴露则刺激NE细胞。具体的 该项目的目标是：1.)为了证明EPI和NE细胞可能是 优先受到刺激。神经介导的肾上腺激活 将由三个生理挑战和 EPI到NE的释放将通过体内延髓技术进行测量 透析2。)评估不同比例的 肾上腺释放的儿茶酚胺对血流动力学的影响 对低血糖、低血压和寒冷暴露的调整。血流动力学 要评估的参数是血压、心输出量、阻力 和血管床的血流分布(使用多普勒血流探头 和放射性标记的微球)。这些实验将在 具有三级交感功能的清醒动物：神经元 破坏(肾上腺髓质完好)，肾上腺脱髓鞘(神经元完好) 和正常动物(肾上腺髓质和神经元完好)。3.)评估 血管紧张素II作为神经递质调节剂的可能性 介导儿茶酚胺释放从而影响EPI比率 并释放了NE。血管紧张素II对血管紧张素转换酶活性的影响 肾上腺髓质释放的EPI和NE的比率 将评估对节前神经的刺激。因此， 拟议的项目应提供重要的新证据，证明机制 存在选择性地控制嗜铬细胞，从而， 更好地了解肾上腺髓质的多样性 对心血管调节的贡献。

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.