Regulation of aldosterone secretion by the renin-angiotensin system during sodium restriction in rats.

Abstract

The role of angiotensin II as mediator of the aldosterone response to short periods of sodium restriction was studied in rats by administration of a converting enzyme inhibitor to block formation of the octapeptide throughout the duration of decreased sodium intake. In control animals, short-term sodium restriction caused increased levels of adrenal receptors for angiotensin II, with enhancement of early and late steps in aldosterone biosynthesis and elevation of plasma aldosterone concentration. Each of these changes induced by sodium deficiency was abolished during blockade of angiotensin II formation by continuous infusion of the converting enzyme inhibitor, SQ 14,225. The absolute dependence of adrenal glomerulosa cell responses on angiotensin H formation indicates that the renin-angiotensin system is the primary regulator of aldosterone secretion during physiological fluctuations in sodium intake.Although the importance of the renin-angiotensin system in the control of aldosterone secretion is well established (1-3), the precise role of angiotensin II in mediating the aldosterone response to sodium deficiency has been more difficult to define (4, 5). While it is generally agreed that the presence of the renin-angiotensin system is essential for the normal aldosterone response to sodium deficiency, there has been controversy about the nature and extent of the actions of angiotensin II as a proximate regulator of zona glomerulosa cells (4, 5). Thus, studies in sheep have suggested that factors other than angiotensin II are involved in the control of aldosterone secretion during sodium depletion and repletion (4).An important question remains about the physiological role of angiotensin II during reduced sodium intake, which is the most frequent stimulus for increased aldosterone secretion under normal conditions in most animal species. Here also a discrepancy has been noted, between the effect of angiotensin II infusions on aldosterone secretion in normal animals and the larger aldosterone responses caused by sodium deficiency (6, 7). However, the sensitivity of the adrenal to angiotensin II in several species increases during sodium restriction (8)(9)(10)(11)(12), and this could contribute to the relatively greater aldosterone secretion that accompanies the increased blood concentrations of angiotensin II during sodium deficiency.The interaction between angiotensin II and altered adrenal sensitivity during the aldosterone response to sodium restriction has been recently analyzed in rats. Initial studies showed that prolonged changes in electrolyte intake were accompanied by altered affinity and concentration of angiotensin II receptors in the rat adrenal (13). In more recent studies during short-term changes in sodium intake, salt restriction for as little as 36 hr increased angiotensin II binding and aldosterone responses inThe costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 ...

Rat model for investigating ACTH-independent angiotensin-induced aldosterone secretion

“…The observation that angiotensin converting enzyme inhibitors suppress the increase in plasma aldosterone following sodium deprivation supports the hypothesis that the renin-angiotensin system plays a primary role in the aldosterone response to sodium deprivation. 23,24 However, it is important to note that in this study we observed a reduction in basal aldosterone levels in NaCl-deprived rats treated with DEX. This reduction was not significant in study A, but this was most likely due to the relatively small number of animals and/or the single DEX injection protocol used in that study.…”

“…22 Their comparatively modest Ang II-induced aldosterone response was most likely due to the relative unresponsiveness of the adrenals in their rats that were fed a standard laboratory chow containing relatively high levels of NaCl. 22,23 Further illustrating the advantage of the dietary regimen and Ang II infusion rate we have determined to be optimal in this study, other investigators have reported even more modest 2-to 6-fold Ang II-induced increases in plasma aldosterone using various other dietary regimens, drug treatments, and Ang II infusion rates. 2,6,7,18 Although some of these investigators did attempt to inhibit Ang II-induced aldosterone secretion with DEX treatment, none of these investigators provided measurements of plasma ACTH in their studies.…”

Effect of adrenomedullin infusion on basal and stimulated aldosterone secretion in conscious sheep with cervical adrenal autotransplants

“…After drastically increasing aldosterone output via mild sodium depletion, ADM did not lower aldosterone secretion in this situation suggesting that, despite having significant inhibitory effects on acutely stimulated ASR, ADM had no role in reducing chronically stimulated aldosterone. Several studies have presented evidence that the steroidogenic response of the zona glomerulosa to sodium depletion is mediated, at least in part, by AngII (Spielman & Davis 1974, Aguilera & Catt 1978. Also, sodium depletion, like AngII, affects aldosterone biosynthesis by altering enzyme activity at a site in both the early (Davis et al 1966) and late (Marusic & Mulrow 1967) biosynthetic pathway.…”

Validation of an integrative mathematical model of dehydration and rehydration in virtual humans

“…Aldosterone, produced by the adrenal glands is stimulated by AII, potassium, and ACTH (Aguilera and Catt 1978). Aldosterone acts in the loop of Henle and distal tubule to promote sodium reabsorption, and in the distal tubule to enhance potassium secretion.…”