SELECTIVE CONTROL OF RELEASE FROM CHROMAFFIN CELLS

选择性控制嗜铬细胞的释放

• 批准号: 2143739
• 负责人: REGIS R VOLLMER
• 金额: $ 14.91万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2143739
• 关键词: adrenal medulla hormone; angiotensin II; blood flow measurement; blood pressure; chromaffin cells; cold temperature; denervation; epinephrine; hemodynamics; hormone regulation /control mechanism; hypoglycemia; hypotension; laboratory rat; neurotransmitter transport; norepinephrine

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.

拟议研究的总体目的是获得更大的 肾上腺髓质在心血管疾病中的作用 调控 实验将在雄性Sprague-Dawley大鼠中进行 为了检验假设：去甲肾上腺素（NE）和 肾上腺素（EPI）从肾上腺释放的变化取决于 自我平衡挑战 此外，儿茶酚胺的比例 释放的重大贡献，以生产适当的 血流动力学调整。 三种生理挑战：低血糖， 选择低血压和寒冷暴露进行研究，因为它们引起 各种各样的心血管适应性。 此外，在初步 研究表明，它们对肾上腺髓质儿茶酚胺的影响不同 释放;低血糖优先引起EPI细胞的释放， 而低血压和冷暴露刺激NE细胞。 具体 该项目的目标是：1。为了证明EPI和NE细胞可能是 优先刺激。 神经介导的肾上腺激活 将引发与三个生理挑战和比例， 将通过体内髓内释放技术测量EPI至NE的释放。 透析2.）为了评估不同比例的 肾上腺释放的儿茶酚胺对血流动力学的影响 调整低血糖、低血压和寒冷暴露。 血流动力 要评估的参数是血压、心输出量、阻力 以及血管床的血流分布（使用多普勒血流探头 和放射性标记的微球）。 这些实验将在 有意识的动物有三个层次的交感神经功能：神经元 破坏（肾上腺髓质完整），肾上腺去髓质（神经元完整） 和正常动物（肾上腺髓质和神经元完整）。3.）第三章评估 血管紧张素II可能作为神经调节剂， 介导的儿茶酚胺释放，从而影响EPI的比例 然后释放。 血管紧张素II对血管生成的影响 肾上腺髓质释放的EPI和NE的比例 评价节前神经支配的刺激。 因此 拟议的项目应提供重要的新证据， 存在嗜铬细胞以被选择性地控制，因此， 更好地了解肾上腺髓质的多样性 有助于心血管调节。