Aldosterone and the Edema of Congestive Heart Failure

Sanders, Louis L.

doi:10.1001/archinte.1964.00280090017004

Cited by 53 publications

(16 citation statements)

References 18 publications

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“…9 In addition to angiotensin II, aldosterone production is under the control of other factors such as potassium and corticotropins, and these may assume greater importance during aldosterone escape. 18 Although it has long been known that aldosterone is important in edema formation, 19 its role in the progression of HF remains unclear. The remarkable result of the RALES trial, which showed a 30% reduction in mortality with the addition of spironolactone in patients with class III and IV HF receiving ACE-I, has renewed interest in the possible pathogenetic role of aldosterone in HF.…”

Section: Discussionmentioning

confidence: 99%

Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure

et al. 2003

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MD; for the Valsartan Heart Failure Trial InvestigatorsBackground-Aldosterone has been implicated in the progression of heart failure. The Valsartan Heart Failure Trial (Val-HeFT) provided the first opportunity to examine the long-term effects of an angiotensin receptor blocker on plasma aldosterone levels in patients with NYHA class II through IV heart failure. Methods and Results-Plasma aldosterone was measured by radioimmunoassay in core laboratories at baseline and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or placebo. In the placebo group, aldosterone (baseline, 150Ϯ160 pg/mL, meanϮSD; nϭ2025) increased at 4, 12, and 24 months. In the valsartan group, aldosterone (baseline, 137Ϯ124 pg/mL, meanϮSD; nϭ2023) decreased at 4 months and remained suppressed for up to 2 years. At end point (last measurement in each patient), mean aldosterone increased by 17.8Ϯ3.0 pg/mL (SEM) (11.9%) in the placebo group and decreased by 23.8Ϯ3.0 pg/mL (SEM) (Ϫ17.4%) in the valsartan group (PϽ0.00001). The effect of valsartan was similar in all subgroups, including those receiving neither ACE inhibitors (ACE-I) nor ␤-blockers (BB) at baseline and those receiving concomitant ACE-I or BB. In contrast, outcome effects varied in the 4 subgroups, with a statistically significant reduction in the combined mortality/morbidity end point in those receiving neither neurohormonal inhibitor and an adverse trend in those treated with both drugs. Conclusions-Valsartan added to background therapy for heart failure produces sustained reduction in plasma aldosterone, consistent with the observed significant reduction in the combined mortality/morbidity end point. A similar reduction in all subgroups based on ACE-I or BB therapy, despite differing clinical outcomes in these subgroups, suggests that aldosterone plasma levels may not be a critical marker of the progression of heart failure. Key Words: heart failure Ⅲ angiotensin Ⅲ trials D espite the remarkable success of ACE inhibitors (ACE-I) in reducing the mortality and morbidity from heart failure (HF), the addition of the aldosterone inhibitor spironolactone was shown to cause an additional 30% decrease in mortality in the Randomized Aldactone Evaluation Study (RALES). 1 Although ACE-I might be expected to reduce aldosterone levels by reducing the stimulating effect of angiotensin II on aldosterone production, recent studies have demonstrated that neither angiotensin II nor aldosterone plasma levels are suppressed chronically by clinically prescribed doses of ACE-I. 2,3 Aldosterone has been implicated as a contributor to structural remodeling of the left ventricle, 4 -6 and the beneficial effects of spironolactone on mortality have been attributed to inhibition of the collagen-generating influence of aldosterone. 7,8 Aldosterone secretion is stimulated by several factors in addition to angiotensin II, and these alternate mechanisms may be important determinants of aldosterone production and its levels in the plasma and tissues in patients with HF. In...

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Section: Discussionmentioning

confidence: 99%

Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure

et al. 2003

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“…This interdependence does not necessarily indicate a cause and effect relationship. Sanders and Melby (30) have provided additional evidence, showing that increased sodium excretion followed the administration of spironolactone in 40%o of their patients with congestive failure. Since all of the cases who responded to the aldosterone antagonist did not excrete increased amounts of aldosterone metabolites in urine, the authors suggested that a reduced rate of removal from plasma may have increased the circulating level of hormone.…”

Section: Methodsmentioning

confidence: 99%

Decreased Plasma Clearance and Hepatic Extraction of Aldosterone in Patients with Heart Failure*

Camargo¹,

Dowdy²,

Hancock³

et al. 1965

J. Clin. Invest.

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“…• Hypersecretion of aldosterone is common in edematous states (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Many patients with congestive heart failure have increased secretion and excretion of aldosterone (1,(3)(4)(5)(6)(7), but patients with edema also have normal rates of secretion, of this hormone (8)(9)(10).…”

Section: Additional Abstractmentioning

confidence: 99%

Plasma Renin in Chronic Experimental Heart Failure and during Renal Sodium "Escape" from Mineralocorticoids

Johnston

Davis

Robb

et al. 1968

Circulation Research

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A striking increase in the plasma renin level occurred in dogs with low output right heart failure secondary to tricuspid insufficiency and pulmonic stenosis and in three of five animals with high output failure produced by a large arteriovenous fistula. When dogs with a small arteriovenous fistula were given daily injections of DOCA, the renal sodium "escape" phenomenon occurred. In these animals, the level of plasma renin was suppressed during DOCA administration both during the initial period of sodium retention and also later when sodium balance was normal or negative. In contrast, when dogs with a larger arteriovenous fistula but without evidence of cardiac failure were given DOCA, they retained sodium and developed signs of congestive heart failure. However, in these animals with congestion and ascites, in contrast to-the dogs that developed spontaneous high output failure, the plasma renin was low. Renin-substrate was unaltered in all of the experimental situations studied except for the decrease observed in dogs with low output right heart failure, la these animals, it seems likely that decreased renin-substrate was secondary to hepatic congestion and liver damage. The renin-angiotensin system does not seem to be related to the "escape" phenomenon, and renin does not appear to be the factor that makes the kidney unusually responsive to mineralocorticoids. Thus, in experimental heart failure the reninangiotensin system was activated, but in the congestive syndrome produced by DOCA the plasma renin level was suppressed. ADDITIONAL KEY WORDSrenin-angiotensin system arteriovenous fistula desoxycorticosterone sodium balance renin-substrate tricuspid insufficiency and pulmonic stenosis high output failure conscious dogs• Hypersecretion of aldosterone is common in edematous states (1-12). Many patients with congestive heart failure have increased secretion and excretion of aldosterone (1, 3-7), but patients with edema also have normal rates of secretion, of this hormone (8-10). Experimental heart failure in dogs is regularly accompanied by an increase in aldosteroneFrom the Departments of Physiology and Surgery, University of Missouri School of Medicine, Columbia, Missouri 6520X.This investigation was supported in part by U. S. Public Health Service Research Grant HE 10612-01 from the National Heart Institute.Dr. Johnston is Research Fellow, National Heart Foundation of Australia.Accepted for publication December 10, 1967. secretion and a high plasma level of aldosterone (2,11,12). The increase in plasma aldosterone in heart failure also results from a decrease in the metabolic clearance of aldosterone by the Ever (4, 9, 13). The present study relates the participation of the reninangiotensin system in experimental heart failure to sodium balance and to the known hypersecfetion of aldosterone. This investigation is also concerned with the role of the renin-angiotensin system in the "escape" phenomenon (14-15). Normal humans or animals given large quantities of a mineralocorticoid retain sodium for only ...

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Aldosterone and the Edema of Congestive Heart Failure

Cited by 53 publications

References 18 publications

Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure

Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure

Decreased Plasma Clearance and Hepatic Extraction of Aldosterone in Patients with Heart Failure*

Plasma Renin in Chronic Experimental Heart Failure and during Renal Sodium "Escape" from Mineralocorticoids

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