What does aldosterone directly increase the reabsorption of?

Aldosterone Directly Increases Sodium Reabsorption

Aldosterone directly increases the reabsorption of sodium (D. Sodium) in the distal tubule and collecting duct of the kidney. 1, 2

Mechanism of Aldosterone Action on Sodium Reabsorption

• Aldosterone acts primarily on the distal tubule and collecting duct of the kidney to regulate fluid balance in the body 2
• In the principal cells of the collecting duct, aldosterone stimulates sodium reabsorption through two main mechanisms:
  • Increases the permeability of the luminal membrane to sodium 2
  • Enhances the activity of the Na/K ATPase pump in the basolateral membrane 2, 3
• Aldosterone increases the cell surface expression of pre-existing Na+ pumps in kidney cortical collecting duct cells within 2-3 hours of exposure 3
• The hormone triggers a 3-fold increase in Na,K-ATPase activity which can be fully accounted for by the increase in Na,K-ATPase cell surface expression (approximately 497%) 3

Molecular Mechanisms of Aldosterone-Mediated Sodium Reabsorption

• Aldosterone regulates the epithelial sodium channel (ENaC) through genomic and non-genomic pathways 4
• The early aldosterone-induced kinase Sgk1 de-represses the surface expression and activity of ENaC by phosphorylating the ubiquitin ligase Nedd4-2, preventing it from ubiquitylating ENaC 4
• Aldosterone also induces expression of the deubiquitylating enzyme Usp2-45, which increases ENaC surface expression and activity by decreasing its ubiquitylation 4
• These mechanisms enhance sodium reabsorption in the distal nephron, leading to increased extracellular fluid volume 5

Clinical Relevance of Aldosterone-Mediated Sodium Reabsorption

• Aldosterone-triggered responses in the collecting duct increase epithelial sodium channel–mediated reabsorption of sodium 1
• This mechanism contributes to diuretic resistance in heart failure patients through distal tubular hypertrophy that increases distal sodium reabsorption 1
• In heart failure, the renin-angiotensin-aldosterone system is activated, leading to increased sodium and water reabsorption, perpetuating the cycle of congestion 1
• Mineralocorticoid receptor antagonists (MRAs) block aldosterone's effect on sodium reabsorption and are part of guideline-directed medical therapy for heart failure 1

Distinguishing Aldosterone from ADH Effects

• While aldosterone directly increases sodium reabsorption, ADH (vasopressin) primarily increases water permeability through aquaporin-2 water channels in the collecting ducts, allowing for free water reabsorption without directly affecting sodium transport 2, 6
• Interestingly, aldosterone can actually decrease vasopressin-stimulated water reabsorption in rat inner medullary collecting ducts through a non-genomic mechanism 7

In summary, aldosterone's primary direct effect is to increase sodium reabsorption in the distal tubule and collecting duct, which indirectly leads to water retention and expansion of extracellular fluid volume.