The pathophysiology of aldosterone in the cardiovascular system.

Published on Sep 1, 2002in Annals of the New York Academy of Sciences5.691
路 DOI :10.1111/J.1749-6632.2002.TB04415.X
John W. Funder87
Estimated H-index: 87
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Abstract
: Until relatively recently, the mineralocorticoid hormone aldosterone was thought to be produced uniquely in the adrenal cortex and to act exclusively on epithelia to promote sodium retention and potassium excretion. However, it is now known that aldosterone also acts on nonepithelial tissues, such as brain, heart, and blood vessels, and that enzymes required for aldosterone biosynthesis are expressed in these same tissues, which may be consistent with local aldosterone production acting in a paracrine fashion. A number of studies indicate that aldosterone exerts clearly deleterious effects when levels are inappropriate for salt status. For example, aldosterone in a high-salt environment initiates a vascular inflammation response that leads to cardiac and vascular pathologies. In experimental models of hypertension and heart failure, the nonepithelial effects of aldosterone are mediated via classical mineralocorticoid receptors, and are largely or completely abolished by administration of the selective aldosterone blocker eplerenone or by reduction of circulating aldosterone by adrenalectomy. In the present manuscript, we review some of the most recent discoveries in the field of aldosterone biology, with special emphasis on the mechanisms involved in the deleterious actions of this mineralocorticoid in cardiovascular tissues.
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#1Karl T. Weber (UTHSC: University of Tennessee Health Science Center)H-Index: 64
The potent mineralocorticoid aldosterone has a multifaceted role in the pathogenesis of congestive heart failure. In addition to its contribution to salt and water retention, it also promotes organ fibrosis. Although angiotensin-converting鈥揺nzyme inhibitors have important therapeutic benefit in heart failure, they do not eliminate the effects of aldosterone. Thus, recent studies have underscored the value of aldosterone-receptor antagonists, such as spironolactone, in the treatment of chronic he...
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The present study explores the possibility of local de novo aldosterone production in normal and failing hearts (human and mouse) and the regulation of such putative cardiac steroidogenesis. Total RNA was isolated from human tissue from failing hearts taken at the time of cardiac transplantation, from normal hearts obtained at autopsy, and from normal and pressure-overloaded mouse hearts. Vascular smooth muscle cells from human artery and vein were also analyzed. RNA was reverse transcribed and ...
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The advent of antihypertensive therapy has resulted in a significant decrease in cardiovascular morbidity and mortality. Nevertheless, the incidence of heart failure, stroke and end-stage renal failure continues to increase. This trend suggests that a mechanism, independent of hypertension, is responsible for end-organ damage. Genetic and experimental models of hypertension have demonstrated that excess aldosterone induces severe injury in the heart, brain and kidneys, and that pharmacological a...
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#1Brian Rayner (UCT: University of Cape Town)H-Index: 34
#2Jonathan E. MyersH-Index: 22
Last. James S. DavidsonH-Index: 27
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Objective. To establish normal ranges for plasma聽aldosterone, renin and aldosterone / renin (A/ R) ratio in聽South African normotensives under typical ou tpatient聽conditions, and to estimate the prevalence of primary聽aldosteronism (PA) among hypertensives in primary care聽settings. Design and methods. One hundred and thirty-six聽normotensive subjects and 154 sex- and age-matched聽hypertensives at three primary care clinics had聽measurements of blood pressure, plasma creatinine,聽K + , aldosterone, pla...
#1Aditi Bhargava (UCSF: University of California, San Francisco)H-Index: 32
#2Meryl J. FullertonH-Index: 17
Last. Tim J ColeH-Index: 156
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Aldosterone plays a major role in regulating sodium and potassium flux in epithelial tissues such as kidney and colon. Recent evidence suggests that serum- and glucocorticoid-regulated kinase (SGK) is induced by aldosterone and acts as a key mediator of aldosterone action in epithelial tissues. Induction of SGK messenger RNA (mRNA) has previously been shown within 30 min of addition of supraphysiological doses of aldosterone to Xenopus A6 cells and within 4 h in rat kidney in vivo. In this study...
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#1Anette Fiebeler (Humboldt University of Berlin)H-Index: 31
#2Folke SchmidtH-Index: 9
Last. Friedrich C. LuftH-Index: 134
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Aldosterone is implicated in cardiac hypertrophy and fibrosis. We tested the role of the mineralocorticoid receptor in a model of angiotensin II鈥搃nduced cardiac injury. We administered spironolactone (SPIRO; 20 mg 路 kg 鈭1 路 d 鈭1 ), valsartan (VAL; 10 mg 路 kg 鈭1 路 d 鈭1 ), or vehicle to rats double transgenic for the human renin and angiotensinogen genes (dTGR). We investigated basic fibroblast growth factor (bFGF), platelet-derived growth factor, transforming growth factor-尾 1 , and the transcrip...
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Continuous angiotensin-converting enzyme (ACE) inhibitor therapy does not necessarily produce significant decreases in plasma aldosterone levels (aldosterone escape). We examined the role of aldosterone escape in 75 essential hypertensive patients treated with an ACE inhibitor (enalapril maleate [34 patients], imidapril hydrochloride [24 patients] or trandolapril [17 patients]) for 40 weeks. With treatment, blood pressure decreased and plasma renin activity increased, while plasma aldosterone co...
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Background 鈥擱ecent reports have indicated that aldosterone is produced in extra-adrenal tissues in animals. The present study was designed to examine whether aldosterone is produced in human heart. Methods and Results 鈥擯lasma levels of aldosterone, BNP, and angiotensin-converting enzyme were measured in anterior interventricular vein (AIV), coronary sinus (CS), and aortic root (Ao), respectively, in 20 patients with left ventricular systolic dysfunction (LVSD), 25 patients with LV diastolic dysf...
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#1Ricardo Rocha (Brigham and Women's Hospital)H-Index: 3
#2Charles T. Stier (NYMC: New York Medical College)H-Index: 23
Last. Gail K. Adler (Brigham and Women's Hospital)H-Index: 71
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To determine the role of aldosterone in mediating cardiovascular damage, we performed ablation/replacement experiments with aldosterone in a rat model of cardiac injury. Administration of angiotensin II and N蠅-nitro-l-arginine methyl ester (L-NAME; nitric oxide synthesis inhibitor) to male rats drinking 1% saline caused hypertension, severe biventricular myocardial necrosis, proteinuria, and fibrinoid necrosis of renal and cardiac vessels. Removal of aldosterone by adrenalectomy or through admin...
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Abstract We have previously demonstrated that manipulation of the renin angiotensin system (RAS) has large effects on digestive efficiency. However, the effects of aldosterone on body weight, adiposity, and glucose absorption in the intestine remains unknown. We here demonstrated that lack of aldosterone synthase (ASKO) in mice did not affect adiposity. In contrast, mice administered with aldosterone were resistant to diet-induced obesity. This is due to gastrointestinal loss of dietary glucose....
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Resistant hypertension is associated with a poor prognosis due to organ damage caused by prolonged suboptimal blood pressure control. The concomitant use of mineralocorticoid receptor (MR) antagonists with other antihypertensives has been shown to improve blood pressure control in some patients with resistant hypertension, and such patients are considered to have MR-associated hypertension. MR-associated hypertension is classified into two subtypes: one with a high plasma aldosterone level, whic...
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Abstract Background Hypertension with hyperaldosteronism could be associated with stroke attributable to endothelial injury. Whether the detrimental effect of aldosterone on stroke among primary aldosteronism patients could be mitigated by administration of mineralocorticoid receptor antagonist or by reduction of aldosterone level via adrenalectomy is still inconclusive. Methods Primary aldosteronism and essential hypertensive patients were enrolled in the Taiwan National Health Insurance from 1...
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#1Katrina M. Mirabito Colafella (Monash University)H-Index: 11
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