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ROLE OF OXYGEN IN ALDOSTERONOGENESIS

氧气在醛固酮生成中的作用

基本信息

批准号：
3244945
负责人：
HERSHEL RAFF
金额：
$ 6.35万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-07-01 至 1994-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3244945
关键词：
aldosterone angiotensins cortisol cow hypoaldosteronism hypoxia oxygen tension oxygenases renal glomerulus renin

项目摘要

The mechanism of the dissociation of renin and aldosterone in hypoxemic states has not been identified. Recent work has suggested that the decrease in aldosterone during hypoxia is due to a direct inhibitory effect of low oxygen on the zona glomerulosa. The long term goal of this project is to determine the sensitivity and mechanism of the effect of oxygen on aldosterone synthesis and secretion. The present study will determine (a) the effect of a full range of PO2 levels (50-450 torr) on aldosterone secretion, (b) the interaction of O2 with CO2 and pH, and (c) the role of 18-hydroxylase in O2-sensitive aldoeteronotenesis. Acutely dispersed bovine zona glomerulosa and fasciculata cells will be incubated at 37 degrees under metal tents through which different gas mixtures are vented. In this way, basal as well as angiotensin and cAMP-stimulated aldosterone and cortisol secretion will be measured under different levels of O2, CO2, and pH. In addition, the effect of oxygen on 18-hydroxylase activity will be determined by measuring the conversion of corticosterone to aldosterone. This work will determine if physiological changes in oxygen directly, specifically and reversibly alter aldosteronogenesis in a O2-level dependent manner and/or by inhibition of 18-hydroxylase activity. Patients with hypoxemia often exhibit fluid and electrolyte disorders possibly in part because they do not exhibit a normal suppression of aldosterone secretion. This may be due to concomitant hypercapnia. Conversely, O2 therapy may be beneficial in the treatment of transient hyperreninemic hypoaldosteronism. Since the penultimate task of the cardiovascular system is the delivery of oxygen to the tissues, the role of oxygen and its delivery in the control of aldosterone is of fundamental basic and clinical importance.

低氧血症时血浆肾素和醛固酮解离机制的研究国家尚未确定。最近的研究表明，在缺氧过程中，醛固酮是由于低的直接抑制作用，球状珊瑚上的氧气该项目的长期目标是确定氧对细胞的影响的敏感性和机制，醛固酮合成和分泌。本研究将确定（a）全范围的PO 2 水平（50-450 μ l）对醛固酮分泌的影响，（B）O2 与CO2和pH值，和（c）18-羟化酶在O2敏感的作用，醛酮不存在。急性分散的牛肾小球囊炎和束状细胞将在37度的金属帐篷下孵育，排出不同的气体混合物。通过这种方式，基底以及血管紧张素和cAMP刺激的醛固酮和皮质醇分泌将在不同水平的O2、CO2和pH值下测量。此外，氧对18-羟化酶活性的影响将通过测量皮质酮向醛固酮的转化。这项工作将确定，如果氧气的生理变化直接、特异性和可逆地改变以O2水平依赖性方式和/或通过抑制 18-羟化酶活性低氧血症患者常表现为液体和电解质紊乱可能部分是因为它们不表现出正常的抑制，醛固酮分泌这可能是由于伴随的高碳酸血症。相反，O2疗法可能有利于治疗短暂性高肾素性低醛固酮症自从2004年的倒数第二个任务以来，心血管系统是氧气输送到组织，的作用，氧及其输送在控制醛固酮中是至关重要的基础和临床重要性。