What is Aldosterone
Aldosterone is a steroid hormone synthesized and secreted by the zona glomerulosa of the adrenal cortex that regulates sodium homeostasis, fluid balance, and blood pressure by binding to mineralocorticoid receptors in the kidney's distal convoluted tubule, causing sodium and water retention while promoting potassium excretion. 1
Physiological Role and Mechanism
Aldosterone acts as a mineralocorticoid hormone that binds to specific receptors at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule, causing increased sodium and water excretion while retaining potassium 2
The hormone is a key component of the renin-angiotensin-aldosterone system (RAAS), which is crucial for blood pressure regulation and fluid-electrolyte balance 3
Aldosterone synthesis in the adrenal gland is modulated by multiple factors including angiotensin II, adrenocorticotropic hormone (ACTH), and serum potassium levels 4, 1
By inducing renal sodium and fluid retention, aldosterone directly increases blood volume and subsequently elevates blood pressure 3
Role in Pregnancy
During normal pregnancy, the RAAS becomes activated with marked increases in plasma renin activity and aldosterone levels by the end of the first trimester, contributing to the 40-50% increase in plasma volume needed to support the growing fetus 3
Increased angiotensinogen production and plasma renin activity lead to elevated angiotensin II production, which mediates increased aldosterone concentrations that stimulate renal sodium and fluid retention 3
Estrogens regulate progressive RAAS activation throughout gestation by directly stimulating angiotensinogen production and increasing ACE2 expression 3
Pathological Excess and Cardiovascular Disease
Elevated aldosterone levels cause hypertension, left ventricular hypertrophy, cardiac fibrosis, and widespread tissue damage through mechanisms independent of blood pressure elevation 5, 6
Excess aldosterone exerts direct toxic effects on renal tubular cells, leading to tubular injury, inflammation, and fibrosis that manifests as increased urinary markers of tubular damage 7
In primary aldosteronism, autonomous and excessive aldosterone production occurs independent of the renin-angiotensin system, affecting 5-10% of all hypertensive patients and up to 20% of those with resistant hypertension 7, 6
Patients with primary aldosteronism have a 12-fold increased risk of target organ damage including kidney injury compared to primary hypertension matched for blood pressure level 7
Clinical Significance in Heart Failure
Aldosterone plays an important pathophysiological role in congestive heart failure, with significantly higher aldosterone secretion in heart failure patients compared to normal individuals 5
Aldosterone promotes myocardial fibrosis through direct, extra-epithelial actions via cardiac mineralocorticoid receptors 8
The RAAS remains chronically activated in heart failure, and aldosterone "escape" may occur through non-angiotensin II dependent mechanisms even with high-dose ACE inhibitor therapy 8
Therapeutic Blockade
Mineralocorticoid receptor antagonists like spironolactone and eplerenone competitively block aldosterone binding at the mineralocorticoid receptor, counteracting the harmful effects of aldosterone excess 2, 4
Eplerenone is indicated for improving survival in stable patients with symptomatic heart failure with reduced ejection fraction after acute myocardial infarction and for treating hypertension 4
Spironolactone acts as both a diuretic and antihypertensive by blocking aldosterone receptors, causing increased sodium and water excretion while retaining potassium 2
The deleterious effects of aldosterone overproduction are often reversible with unilateral laparoscopic adrenalectomy or treatment with mineralocorticoid receptor antagonists 7