Sodium depletion, hypovolaemia or both were induced in potassium-depleted rats by various experimental protocols in order to study mechanisms involved in the regulation of late steps in aldosterone biosynthesis. The relative effects of such manoeuvres upon aldosterone biosynthesis and upon the plasma renin activity were compared. The conversion of corticosterone to aldosterone by incubated adrenal glands could be stimulated by a factor of 3 to 4 within 48 h by each of the following procedures: feeding on a sodium\x=eow-\ and potassium-deficient diet or on sucrose, water restriction or treatment with furosemide. A 20-fold stimulation was elicited by experimental oedema due to subcutaneous polyethylene glycol solution or formalin. Intermediate responses were obtained by combining the sodium-and potassium-deficient diet with either water restriction or furosemide treatment as well as by the infusion of angiotensin II. Significant increases in the plasma renin activity, which were however not proportional to the stimulation of aldosterone biosynthesis, were seen in rats kept on the sodium-and potassium-deficient diet or treated by furosemide, polyethylene glycol or formalin, but not in rats kept on sucrose or deprived of water. An elevation in the plasma potassium concentration was observed only in the animals treated with water restriction. These results indicate that during potassium deficiency the stimulation of late steps in aldosterone biosynthesis by sodium and water depletion is mediated by the renin-angiotensin system and by an unknown mechanism which enhances the sensitivity of the zona glomerulosa to angiotensin II. Experimental oedema in potassium-deficient rats seems to be a useful model for further investigations of this mechanism.
The role of angiotensin II in the stimulation of aldosterone biosynthesis by sodium sequestration in potassium-deficient rats was assessed by experiments involving 1-day angiotensin II infusion, converting enzyme inhibition, and bilateral nephrectomy. In intact rats, only an extremely high dose of exogenous angiotensin II imitated the stimulatory effects of polyethylene glycol-induced edema on the conversions of deoxycorticosterone and corticosterone to 18-hydroxycorticosterone and aldosterone. Treatment with the converting enzyme inhibitor captopril as well as bilateral nephrectomy blocked the aldosterone-stimulating action of edema. This inhibition was prevented by the simultaneous infusion of angiotensin II in captopril-treated rats but not in nephrectomized animals. According to these results, angiotensin II is an essential mediator in the stimulation of aldosterone biosynthesis by sodium sequestration. However, the role of the kidneys appears to be twofold. First, they act through the secretion of renin. In addition, a second yet unknown kidney factor is necessary for a full response of the zona glomerulosa to the stimulatory action of angiotensin II.
The role of the kidneys in the stimulation of aldosterone biosynthesis by sodium sequestration was investigated in potassium-depleted rats. After 2 wk on a potassium-deficient diet, rats were treated by subcutaneous injections of polyethylene glycol or formalin and were then kept on sucrose and water for 24 h. Either type of experimental edema markedly enhanced the conversions of tritiated deoxycorticosterone and corticosterone to aldosterone and 18-hydroxycorticosterone by incubated capsular portions of the adrenal glands and partially normalized the deranged pattern of endogenous corticosteroid output in response to serotonin. Bilateral nephrectomy completely blocked these effects of edema on the zona glomerulosa. When uremia was induced by bladder resection, with the kidneys left intact, edema still significantly stimulated aldosterone biosynthesis. Irrespective of increases in the plasma creatinine, the plasma potassium remained at uniformly low levels in all experimental groups of animals. According to these observations, experimental edema stimulates late steps of aldosterone biosynthesis in potassium-depleted rats by mediation of the kidneys, most likely through the renin-angiotensin system.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.