What is the primary site of action of aldosterone in the kidney?

Site of Action of Aldosterone

The primary site of action of aldosterone is the distal renal tubules and collecting ducts, where it stimulates sodium reabsorption and potassium secretion through binding to mineralocorticoid receptors. 1, 2

Mechanism of Action

Aldosterone acts through the following mechanisms:

• Distal Tubule Effects:

  • Binds to mineralocorticoid receptors in the distal convoluted tubule 2
  • Increases sodium reabsorption through the sodium chloride cotransporter 2
  • Contributes to hypertrophy and hyperplasia of distal tubular cells in conditions like heart failure 2

• Collecting Duct Effects:

  • Increases sodium reabsorption via epithelial sodium channels (ENaC) 2
  • Stimulates the Na/K ATPase pump in the basolateral membrane 2
  • Promotes potassium secretion into the tubular lumen 1
  • Causes hypertrophy of principal and intercalated cells 2

Pharmacological Evidence

The site of action is confirmed by pharmacological evidence:

• Spironolactone and eplerenone are specific antagonists of aldosterone that act primarily through competitive binding at the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule 1, 3

• Mineralocorticoid receptor antagonists are more effective than loop diuretics in managing conditions with hyperaldosteronism, confirming the importance of the distal tubule and collecting duct as primary sites of action 2

Physiological Significance

Understanding aldosterone's site of action is critical because:

• In heart failure and cirrhosis, increased aldosterone leads to sodium retention primarily through its effects on the distal nephron 2

• In primary hyperaldosteronism, autonomous aldosterone production causes sodium reabsorption in the renal cortical collecting duct, leading to extracellular fluid volume expansion and hypertension 2

• Aldosterone's effects on the distal tubule and collecting duct explain why mineralocorticoid receptor antagonists are effective in managing conditions with fluid overload 2

Additional Considerations

While the primary site of action is the distal tubule and collecting duct, research has identified other effects:

• Some evidence suggests aldosterone may also stimulate NHE3 in renal proximal brush borders, potentially affecting proximal tubular sodium reabsorption 4, but this is not its primary site of action

• Aldosterone can have rapid "non-genomic" actions that are independent of transcription and translation, mediated by distinct receptors 5

• Protein kinase signaling cascades can be rapidly activated by aldosterone in various tissues 6

Therefore, based on the most recent and highest quality evidence, the correct answer is (b) distal renal tubules, with additional effects on (c) collecting ducts.