REGULATION OF ADRENAL MEDULLARY/CORTICAL BLOOD FLOW

肾上腺髓质/皮质血流的调节

• 批准号: 3082450
• 负责人: MICHAEL J BRESLOW
• 金额: $ 6.48万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3082450
• 关键词: ACTH inhibitor; acetylcholine; adenine nucleotides; adrenal glands; adrenal medulla; adrenocorticotropic hormone; anticholinergic agent; blood flow measurement; catecholamines; chromaffin cells; cortisol; denervation; dogs; hemorrhagic shock; hormone regulation /control mechanism; neurotransmitter biosynthesis; physiologic stressor; radioimmunoassay; secretion; steroid hormone biosynthesis; vasodilation

The candidate received residency training in both Internal Medicine and Anesthesiology, and subspecialty training in Critical Care Medicine, and joined the faculty of Johns Hopkins Hospital 3 years ago as Associate Director of the Surgical Intensive Care Unit. In addition to administrative, patient care and teaching activities, the candidate has participated in physiology research projects investigating adrenal blood flow regulation, and regional perfusion during endotoxin shock. This work resulted in development of a radiolabelled microsphere technique for separate measurement of adrenal medullary and cortical blood flow. Data obtained with this technique indicate that blood flow to the medulla and cortex may be independently regulated, and that stimuli which elicit medullary and cortex secretory activity are associated with vasodilation, particularly in medulla where blood flow increases several-fold even during hemorrhagic hypotension. No other organ is known to demonstrate increased blood flow with reduction of arterial blood pressure, and investigation into mechanisms responsible for this marked vasodilation will constitute the first Specific Aim of the Research Plan. In these experiments the effect of muscarinic, nicotinic, adrenergic and adenosine receptor antagonists on nerve stimulation-induced medullary vasodilation, will be used to differentiate neurotransmitter mediated vasodilation from chromaffin granule content-mediated vasodilation. In Specific Aim 2, potential physiologic implications of increased medullary blood flow during catecholamine secretion will be investigated. Experiments to determine whether increased medullary blood flow is necessary for maximal catecholamine secretion will be performed, and mechanisms of blood flow effects on catecholamine secretion will be evaluated. Specific Aim 3 will determine whether cortical blood flow increases during cortisol synthesis and secretion, using exogenously administered ACTH as an adrenocortical activator. Specific inhibitors of cortisol synthesis will be used to determine whether ACTH-induced cortical vasodilation is coupled with cortical synthetic activity. Little is known concerning regulation of blood flow and metabolism in endocrine tissues, and the studies outlined in this grant proposal should provide new insights into the physiology of these two important endocrine organs.

候选人在内部和外部都接受了住院医师培训 医学和麻醉学，以及危重病专科培训 护理医学，并加入了约翰霍普金斯医院3教员 几年前作为外科重症监护室的副主任 单位 除了行政、病人护理和教学外， 活动，候选人参加了生理学研究 研究肾上腺血流调节的项目， 内毒素休克期间的灌注。 这项工作导致 放射性标记微球技术的发展， 分别测量肾上腺髓质和皮质血 流 用这种技术获得的数据表明， 对髓质和皮质的影响可以独立调节， 刺激引起髓质和皮质分泌活动 与血管舒张有关，特别是在髓质， 即使在出血期间， 低血压 据了解，没有其他器官表现出增加 血流减少，动脉血压降低，以及 对造成这一情况的机制进行调查， 血管舒张将构成研究的第一个具体目标 计划 在这些实验中，毒蕈碱，烟碱， 肾上腺素能和腺苷受体拮抗剂 刺激诱导的髓质血管舒张，将用于 区分神经递质介导的血管扩张与 嗜铬颗粒含量介导的血管舒张。 在特定 目的2，髓内增加的潜在生理意义 将研究儿茶酚胺分泌期间的血流。 实验以确定是否增加髓血流量 是最大的儿茶酚胺分泌所必需的 进行，和机制的血流影响， 将评价儿茶酚胺分泌。 第3章将 确定皮质血流量是否增加皮质醇 合成和分泌，使用外源性给予的促肾上腺皮质激素作为 肾上腺皮质激活剂 皮质醇特异性抑制剂 合成将用于确定是否ACTH诱导的 皮质血管舒张与皮质合成活性相结合。 关于血流的调节知之甚少， 内分泌组织中的代谢，以及本研究中概述的研究 拨款提案应提供新的见解， 这两个重要的内分泌器官。