Aldosterone, mineralocorticoid receptors, and vascular inflammation.
OBJECTIVE
Aldosterone and its mineralocorticoid receptor represent an ancient signaling system. Indeed, the mineralocorticoid receptor is older than its agonist. Both have probably served various functions through the eons and salt preservation may be relatively recent. A large body of evidence suggests that aldosterone conducts signaling in vascular cells and contributes substantially to vascular remodeling and target organ damage. A blood pressure and salt balance-independent effect was first observed in two large heart failure trials.


RESULTS
Mineralocorticoid receptor blockade has now been shown to reduce proteinuria even in the face of angiotensin converting enzyme inhibition and AT1 receptor blockade. Mineralocorticoid receptor blockade effectively reduces target organ damage in every hypertensive model tested, irrespective of circulating renin and aldosterone levels. Protection is also observed in nonhypertensive diabetic and hyperlipidemic models. Signaling in vascular cells involves primarily the mitogen activated protein kinase pathway with participation of the epidermal growth factor receptor. Novel signaling molecules have been shown to participate in aldosterone-mediated actions including the murine double-minute type 2 protein that participates in antiapoptotic and proliferative effects. Clinically, mutations in the mineralocorticoid receptor have shed additional light on its importance.


CONCLUSIONS
A resurgence of interest in aldosterone reflects its importance and clinical relevance for vascular remodeling and target organ damage.
Fiebeler
Anette
A
Medical Faculty of the Charité, Max Delbrück Center for Molecular Medicine, Franz Volhard Clinic, HELIOS Klinikum, Berlin, Germany. fiebeler@charite.de
Muller
Dominik N
DN
Shagdarsuren
Erdenechimeg
E
Luft
Friedrich C
FC
D000450:Aldosterone / Q000502:physiology*; D000818:Animals; D001808:Blood Vessels / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D012083:Renin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D017382:Reactive Oxygen Species; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D012083:Renin