Aldosterone concentrations are inappropriately high in many patients with hypertension, as well as in an increasing number of individuals with metabolic syndrome and sleep apnoea. A growing body of evidence suggests that aldosterone and/or activation of the MR (mineralocorticoid receptor) contributes to cardiovascular remodelling and renal injury in these conditions. In addition to causing sodium retention and increased blood pressure, MR activation induces oxidative stress, endothelial dysfunction, inflammation and subsequent fibrosis. The MR may be activated by aldosterone and cortisol or via transactivation by the AT1 (angiotenin II type 1) receptor through a mechanism involving the EGFR (epidermal growth factor receptor) and MAPK (mitogen-activated protein kinase) pathway. In addition, aldosterone can generate rapid non-genomic effects in the heart and vasculature. MR antagonism reduces mortality in patients with CHF (congestive heart failure) and following myocardial infarction. MR antagonism improves endothelial function in patients with CHF, reduces circulating biomarkers of cardiac fibrosis in CHF or following myocardial infarction, reduces blood pressure in resistant hypertension and decreases albuminuria in hypertensive and diabetic patients. In contrast, whereas adrenalectomy improves glucose homoeostasis in hyperaldosteronism, MR antagonism may worsen glucose homoeostasis and impairs endothelial function in diabetes, suggesting a possible detrimental effect of aldosterone via non-genomic pathways.
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Review Article| August 13 2007
Aldosterone and end-organ damage
Annis M. Marney;
Nancy J. Brown
1Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Vanderbilt University Medical Center, 550 Robinson Research Building, Nashville, TN 37232-6602, U.S.A.
Correspondence: Professor Nancy J. Brown (email Nancy.firstname.lastname@example.org).
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Publisher: Portland Press Ltd
Received: April 04 2007
Revision Received: May 09 2007
Accepted: May 16 2007
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2007 Biochemical Society
Annis M. Marney, Nancy J. Brown; Aldosterone and end-organ damage. Clin Sci (Lond) 1 September 2007; 113 (6): 267–278. doi: https://doi.org/10.1042/CS20070123
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