Review
Published: 2017-09-15

Regulation of aldosterone in heart failure and vascular aging: implications for therapy

Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA
Adrenocortical zona glomerulosa cell Aldosterone Angiotensin II type 1 Receptor Barrestin-1, Heart Failure Vascular aging

Abstract

Aldosterone mediates a multitude of angiotensin II (AngII)’s effects. Its synthesis and secretion from the zona
glomerulosa cells of the adrenal cortex, elevated in chronic heart failure (HF), is induced by AngII type 1 receptors
(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupled to Gq/11 proteins. However, it also signals
through barrestin-1 (barr1) or -2 (barr2), both of which mediate G protein-independent signaling. Over the past
decade, a second, Gq/11 protein-independent but barr1-dependent signaling pathway emanating from the adrenocortical
AT1R and leading to aldosterone production has come to the light, signifying that AT1R antagonists
that block both G proteins and barrs at the AT1R equally well are needed to achieve full suppression of aldosterone.
Indeed, although all marketed angiotensin receptor blockers (ARBs, AT1R antagonists or sartans) potently
inhibit G protein activation, candesartan and valsartan were found to be the most potent agents at blocking also
barr activation. Therefore, these two drugs are portended to be the most effective aldosterone suppressors
in vitro and in vivo in post-myocardial infarction (MI) HF animals. Finally, in addition to HF, hypertension, and
other cardiovascular diseases, aldosterone is implicated also in arterial aging and associated vascular fibrosis,
making it a potential therapeutic target for cardiovascular disease treatment in geriatric patients

Affiliations

A. Lymperopoulos

Laboratory for the Study of Neurohormonal Control of the Circulation, Department of Pharmaceutical Sciences (Pharmacology), College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA

Copyright

© Società Italiana di Gerontologia e Geriatria (SIGG) , 2017

How to Cite

[1]
Lymperopoulos, A. 2017. Regulation of aldosterone in heart failure and vascular aging: implications for therapy. JOURNAL OF GERONTOLOGY AND GERIATRICS. 65, 03 Special (Sep. 2017), 206-211.
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