Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis.

Brown NJ
Nat Rev Nephrol. 2013 9 (8): 459-69

PMID: 23774812 · PMCID: PMC3922409 · DOI:10.1038/nrneph.2013.110

The steroid hormone aldosterone regulates sodium and potassium homeostasis. Aldosterone and activation of the mineralocorticoid receptor also causes inflammation and fibrosis of the heart, fibrosis and remodelling of blood vessels and tubulointerstitial fibrosis and glomerular injury in the kidney. Aldosterone and mineralocorticoid-receptor activation initiate an inflammatory response by increasing the generation of reactive oxygen species by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and mitochondria. High salt intake potentiates these effects, in part by activating the Rho family member Rac1, a regulatory subunit of reduced NADPH oxidase that activates the mineralocorticoid receptor. Studies in mice in which the mineralocorticoid receptor has been deleted from specific cell types suggest a key role for macrophages in promoting inflammation and fibrosis. Aldosterone can exert mineralocorticoid-receptor-independent effects via the angiotensin II receptor and via G-protein-coupled receptor 30. Mineralocorticoid-receptor antagonists are associated with decreased mortality in patients with heart disease and show promise in patients with kidney injury, but can elevate serum potassium concentration. Studies in rodents genetically deficient in aldosterone synthase or treated with a pharmacological aldosterone-synthase inhibitor are providing insight into the relative contribution of aldosterone compared with the contribution of mineralocorticoid-receptor activation in inflammation, fibrosis, and injury. Aldosterone-synthase inhibitors are under development in humans.

MeSH Terms (20)

Aldosterone Animals Aromatase Inhibitors Cardiovascular System Cytochrome P-450 CYP11B2 Endothelial Cells Fadrozole Fibrosis Humans Imidazoles Inflammation Kidney Macrophages Mineralocorticoid Receptor Antagonists Myocardium Myocytes, Cardiac Pyridines Reactive Oxygen Species Receptors, Mineralocorticoid Sodium, Dietary

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