Settings of increased aldosterone activity – obesity,
advanced age and disease
The MR is expressed in adipose tissue, driving stem cell differentiation
and leptin secretion and contributes to Metabolic Syndrome in obesity.
Leptin induces release of aldosterone in a positive feedback loop and
may be a significant mediator of obesity-associated hyper-aldosteronism.
MR-driven hypertrophic adipocytes, especially in visceral and
perivascular fat, modulate vascular health and disease through release
of proinflammatory cytokines, IL-1, Il-6, TNFa and
monocyte-chemotactic-protein-1 (MCP-1) and pro-thrombotic factor
plasminogen activator inhibitor type-1 (PAI-1). (11,12)
Aging is characterized by a transition from physiological aldosterone
regulation to a pattern of renin-independent secretion. The adrenal
gland shows increasing non-neoplastic foci of aldosterone-producing
cells while cortisol-mediated MR activation increases. MR expression has
also been shown to be increased in the vasculature with aging. Thus, the
elderly may have increased risk of autonomous aldosterone production,
cortisol-mediated MR activation, and increased MR expression, all
contributing to increased aldosterone-mediated pathogenesis.
Evidence continues to accrue confirming chronic Ang II/aldosterone/MR
hyper-activation in several cardiovascular disorders, including
hypertension, coronary artery disease, ventricular hypertrophy, atrial
fibrillation, congestive heart failure and related diseases such as
chronic kidney disease, diabetes, stroke and Metabolic Syndrome. (13) In
these disease settings the affected tissues are in a heightened state of
oxidative and inflammatory stress with persistent interactive
up-regulation promoting disease progression. The homeostatic response to
chronic RAAS stress is up-regulation of ACE2 and atrial and brain
natriuretic factors. The most common medical interventions include ACE
inhibitors (ACEI), ATR blockers (ARB) and statins, with MR blockers
(MRB) reserved for end-stage disease. Abrupt discontinuation of these
medications is associated with rapid increase in disease and death in
patients after myocardial infarction or in cardiac failure. During acute
events such as myocardial infarction and viral pneumonia, attenuating
the RAAS stress response has been shown to be protective.