Renal & Adrenal Endocrinology — RAAS

Renin-Angiotensin-Aldosterone system primarily for hormonal regulation of blood volume.

Renin

• Proteolytic enzyme
• Secreted from granula cells in juxtaglomerular apparatus
• Secretion:
  • Stimulated by:
    • ↓ GFR
    • ↓ tubular Na/Cl at macula densa
    • β1 SNS stimulation of granular cells
    • ↑ prostacyclin levels
    • ↓ levels of angiotensin 2 or ADH
  • Inhibited by:
    • ↑ renal perfusion pressure
    • ↑ sodium delivery to DCT
    • ↑ by ATII and ADH
• Target:
  • circulating angiotensinogen
• Effects:
  • Tubular effects:
    • ↑’d PCT Na/Cl reabsorption, ↑’d tubular K secretion
    • Direct PCT effect
    • Aldosterone release
  • Volume Status effects:
    • ↑’d total body water via
    • ↑’d thirst (hypothal)
    • ↑’d ADH secretion
  • Renal Blood flow effects
    • Direct: Reduced RBF and GFR (Aff>Eff)
    • ↑’d renin → ↑ AT2 (see AT2 below) → ↑’d Aldosterone
    • Vasoconstriction (aff=eff)
    • Mesangial cell contraction

Angiotensin 2

• Production:
  • Angiotensinogen is the precursor peptide hormone produced by the liver
  • Angiotensin 1 (decapeptide)
    • ↑ Renin by JGA (above) → cleavage of Angiotensinogen → AT1
    • No biological activity
  • Angiotensin 2 (octapeptided)
    • Angiotensin Converting Enzyme (ACE) in pulmonary capil endothelia
    • → ↑AT2
  • Angiotensin 3 (septapeptide)
    • 40% of the pressor activity AT2
    • 100% of the aldosterone-producing activity
  • Angiotensin 4 (hexapeptide)
    • Minimal biological activity
• Target:
  • Mesangial cells, arteriolar SM, CNS, posterior pituitary
  • AT1 and AT2 receptors
  • Acts via GPCR (Gq via PLC to increase IP3 and intracellular Ca)
• Effect:
  • CVS
    • Vasopressor
    • Resets baroreceptor control of HR at higher pressure
    • Potent mitogen for smooth muscle and cardiac myocytes
    • Direct positive inotrope
  • CNS
    • ↑’d sympathetic outflow
    • ↑’d thirst
    • ↑’d ADH release from posterior pituitary.
  • Renal
    • Negative feedback on renin release
    • ↑’d aldosterone release
    • ↓’d RBF and GFR
      • Direct renal arteriole constriction (efferent = afferent)
      • Mesangial cell contraction thus ↓’d Kf and GFR
    • ↑’d sodium/chloride reabsorption in PCT
      • Direct effect and via ↑’d aldosterone release

Aldosterone

• Steroid Hormone
• Source:
  • Adrenal cortex (zona glomerulosa)
• Release Stimuli:
  • adrenal cortical hyperkalaemia
  • ↑’d AT2
  • ↑’d ACTH
• Target:
  • Distal collecting duct and CCD principal cells ENaC receptors.
  • Na/K ATPase co-transporters in DCT/CCD, GIT and secretory glands
• Effect:
  • Sodium (↑’d plasma Na)
    • Upregulates basolateral ENaC and Na/K ATPase to increase Na reabsoption
    • ↑’d Na reabsorption throughout the GIT/sweat and salivary glands via Na/K ATPase
    • ↑’d H2O reabsorption and ↑’d Na via solvent drag
  • Potassium (↓’d plasma K)
    • ↑’d K secreation at DCT/CCD principal cells (via ROMK)
    • ↑’d K secretion throughtout the GIT/Salivary glands
    • ↑’d intracellular K uptake
  • Chloride (↑’d plasma Cl)
    • ↑’d Cl uptake in distal tubule
  • Acid (H) Effects
    • Upregulation of H and H/K-ATPase in type A intercalated cells of CCD
    • Increases H secretion (and HCO3 reabsorption)

Gladwin 2016

Answer by Gladwin