REGULATION OF ADRENAL MEDULLARY/CORTICAL BLOOD FLOW

肾上腺髓质/皮质血流的调节

• 批准号: 3082448
• 负责人: MICHAEL J BRESLOW
• 金额: $ 6.39万
• 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/3082448
• 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.

候选人接受了内部住院医师培训 医学和麻醉学以及重症亚专业培训 护理医学，并加入约翰·霍普金斯医院 3 几年前担任外科重症监护室副主任 单元。 除了行政、病人护理和教学之外 活动，候选人参加过生理学研究 研究肾上腺血流调节和区域性的项目 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开发 肾上腺髓质和皮质血的单独测量 流动。 通过该技术获得的数据表明血流 髓质和皮质可以独立调节，并且 引起髓质和皮质分泌活动的刺激 与血管舒张有关，特别是在髓质中 即使在失血期间，血流量也会增加数倍 低血压。 目前尚无其他器官显示出增加的 血流量降低，动脉血压降低，以及 调查造成这一现象的机制 血管舒张将构成该研究的第一个具体目标 计划。 在这些实验中，毒蕈碱、烟碱、 神经肾上腺素能和腺苷受体拮抗剂 刺激引起的髓质血管舒张，将用于 神经递质介导的血管舒张与 嗜铬颗粒含量介导的血管舒张。 具体来说 目标 2，髓质增加的潜在生理影响 将研究儿茶酚胺分泌期间的血流。 确定髓质血流量是否增加的实验 是儿茶酚胺最大分泌所必需的 进行，以及血流影响的机制 将评估儿茶酚胺的分泌。 具体目标 3 将 确定皮质醇期间皮质血流量是否增加 合成和分泌，使用外源性 ACTH 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 ACTH 是否诱导 皮质血管舒张与皮质合成活动相结合。 关于血流和血流的调节知之甚少 内分泌组织的代谢，以及本文概述的研究 拨款提案应提供对生理学的新见解 这两个重要的内分泌器官。