Title: Aldosterone, Mineralocorticoid Receptor and the Metabolic Syndrome:Role of the Mineralocorticoid Receptor Antagonists
Volume: 10
Issue: 2
Author(s): Vanessa Ronconi, Federica Turchi, Gloria Appolloni, Valentina di Tizio, Marco Boscaro and Gilberta Giacchetti
Affiliation:
Keywords:
Aldosterone, metabolic syndrome, mineralocorticoid receptor, mineralocorticoid receptor antagonists, primary aldosteronism, obesity, pancreatic fibrosis, impaired beta cell function, oxidative stress, inflammation
Abstract: Several lines of evidence suggest a detrimental effect of aldosterone excess on the development of metabolic alterations. Glucose metabolism derangements due to aldosterone action are frequently observed not only in patients with primary aldosteronism but also in patients with obesity. A contribution to the hyperaldosteronism observed in obese subjects can be attributed, at least in part, to the action of still unidentified adipocyte-derived factor. Aldosterone, through genomic and non-genomic actions contributes to induce several abnormalities: pancreatic fibrosis, impaired beta cell function, as well as reduced skeletal muscle and adipose tissue insulin sensitivity. Oxidative stress, systemic inflammation, together with these metabolic alterations may explain the appearance of the cardiometabolic syndrome and the progression of cardiovascular and renal diseases, in the presence of inappropriate aldosterone levels. The biological actions of aldosterone are mediated by mineralocorticoid receptor (MR), although MR can be activated through an aldosteroneindependent fashion. Besides salt-water homeostasis, MR activation promotes inflammation, endothelial dysfunction, cardiovascular remodelling and affects adipose tissue differentiation and function.
Clinical and experimental studies have shown that MR blockade is able to suppress inflammation, to improve endothelium- dependent vasorelaxation, but most interestingly, to improve pancreatic insulin release as well as insulin-mediated glucose utilization. These actions indicate MR antagonists as a useful therapeutic tool able not only to reduce cardiovascular risk and renal damage, but also to improve metabolic sequaelae.
