ADRENAL ANGIOTENSIN SECRETION--NORMAL/HYPERTENSIVE RATS

肾上腺血管紧张素分泌——正常/高血压大鼠

• 批准号: 2460028
• 负责人: IMRE KIFOR
• 金额: $ 19.95万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2460028
• 关键词: adrenal glands; aldosterone; angiotensin /renin /aldosterone hypertension; angiotensin II; brefeldin A; dietary potassium; dietary sodium; hormone regulation /control mechanism; laboratory rat; peptidyl dipeptidase A; renal glomerulus; secretion; single cell analysis

DESCRIPTION: (Adapted from investigator's abstract) Abnormalities in the response of the renin-angiotensin-aldosterone axis to changes in sodium intake have been proposed as an etiologic factor in both experimental and human hypertension. Of particular relevance to this subject is the potential role of the local adrenal renin-angiotensin system, whose presence has clearly have been established, in modulating aldosterone output with changes in dietary electrolyte content. Yet, unclear from the presently-available studies are the answers to several critical questions: (A) Is the angiotensin II (Ang II) secreted via a regulated pathway? If so, then the release of active renin, angiotensinogen, and converting enzyme are byproducts of the primary secreted product, Ang II. (B) How does sodium intake modify Ang II production? Five not necessarily mutually-exclusive hypotheses will be tested. Sodium restriction increases Ang II production by 1) increasing renin synthesis, 2) increasing converting enzyme activity or production, 3) increasing angiotensinogen production, 4) decreasing intracellular Ang II degradation, or 5) increasing the number of Ang II secreting cells or the amount of Ang II produced by each cell. Three tools will be used to address these hypotheses, including Brefeldin A pretreatment, measuring the accumulation of different angiotensin peptides in the cells, and measuring the Ang II secretion from single glomerulosa cells obtained from sodium loaded or sodium restricted rats. (C) The investigator will determine the relationship between aldosterone and Ang II production by isolated glomerulosa cells. The primary questions to be addressed include: 1) Are aldosterone and Ang II produced by the same cell? 2) What fraction of glomerulosa cells produce Ang II and/or aldosterone? 3) Are aldosterone and Ang II production from individuals cells similar? and, 4) What effect do changes in dietary potassium and sodium have on the output of aldosterone from single cells? Over the past several months, the applicants have established techniques to measure both Ang II and aldosterone production from single glomerulosa cells, and to measure the rate of precursor (prorenin, angiotensinogen, etc.), and intracellular angiotensin I (Ang I), Ang II and active renin production. With these technical breakthroughs they can now design experiments to specifically address these questions. With this information available, a clearer understanding of the regulation of aldosterone secretion will be available, which is particularly important in understanding the pathophysiology of hypertension where its regulation has been reported to be altered.

描述：（改编自研究者摘要）摘要 在肾素-血管紧张素-醛固酮轴对变化的反应中 钠摄入量的增加被认为是这两种疾病的致病因素。 实验和人类高血压。与此特别相关的是 受试者是局部肾上腺肾素-血管紧张素 系统，其存在显然已经建立，在调节 膳食电解质含量变化与醛固酮分泌量的关系。 然而， 目前的研究还不清楚以下问题的答案 几个关键问题：（A）血管紧张素II（Ang II）是否分泌 通过一个受监管的途径？ 如果是这样，那么活性肾素的释放， 血管紧张素原和转化酶是初级代谢的副产物。 分泌产物，血管紧张素II。(B)钠摄入如何改变血管紧张素II 制作？五个不一定相互排斥的假设 会得到考验 钠限制增加血管紧张素II的生产， 1)增加肾素合成，2）增加转化酶 活性或产生，3）增加血管紧张素原产生， 4)减少细胞内Ang II降解，或5）增加细胞内Ang II降解， 血管紧张素II分泌细胞的数量或血管紧张素II产生的量 每个细胞。将使用三种工具来解决这些假设， 包括Brefeldin A预处理，测量 不同的血管紧张素肽在细胞中，并测量血管紧张素 II从钠获得的单个肾小球细胞的分泌 高负荷或钠限制的大鼠。 (C)研究者将 确定醛固酮和血管紧张素II产生之间的关系 分离的肾小球细胞。 需要解决的主要问题 包括：1）醛固酮和血管紧张素II是否由同一细胞产生？（二） 哪部分肾小球细胞产生血管紧张素II和/或醛固酮？ 3)醛固酮和血管紧张素II是由单个细胞产生的吗 相似吗以及，4）膳食中钾和钠的变化 对单细胞分泌醛固酮有什么影响过去 几个月来，申请人已经建立了技术， 同时测量血管紧张素II和醛固酮的产生， 肾小球细胞，并测量前体（原肾素， 血管紧张素原等），和细胞内血管紧张素I（Ang I）， II和活性肾素生产。 这些技术 他们现在可以设计实验来专门解决 这些问题。 有了这些信息，更清晰的 了解调节醛固酮分泌将是 这一点对于理解 高血压的病理生理学，其调节已经 据报道，被篡改。