ADRENAL ANGIOTENSIN SECRETION--NORMAL/HYPERTENSIVE RATS

描述：（改编自研究者摘要）异常

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.