Antihypertensive

Master answer

Angiotensinogen

• Cleaved by renin         
• release from juxtaglomerular cells:
  • Lowered renal arterial pressure
  • Less NaCl (more about Cl^–) past macula densa
  • Sympathetic nervous system activation

Angiotensin I

• Converted by ACE to Angiotensin II

Angiotensin II

• Actions:  Via AT₁ receptors (AT₂ receptors have unclear significance)
• Renal:
  • Afferent and renal artery vasoconstriction (weaker)
  • Efferent vasoconstriction (stronger)
  • Constricts mesangial cells (decrease GFR)
  • Increased sodium and water resorption
    •             -> Na⁺/H⁺ antiporter
    •             -> Decreased hydrostatic pressure in capillary (Starling force)
• Vascular:
  • Widespread vaso and veno constriction
  • Promotes hyperplasia
• Cardiac
  • Promotes hyperplasia
• Neural:
  • Directly increases noradrenaline release from presynaptic membrane
  • Stimulates catecholamine release
• Promotes aldosterone release
• Degrades bradykinin
  • So less NO, cAMP -> less vasodilation

Aldosterone

• Increases activity of Na⁺/H⁺ antiporter, Na⁺/K⁺ ATPase in the distal convoluted tubule and collecting duct -> water retention
• There is also an ACE independent pathway to angiotensin II formation

ACE inhibitors:

• Block ACE
• Reduce afterload
• Modulate cardiac sympathetic stimulation
• Inhibit cardiac and vascular hypertrophy
• Cause cardiac remodelling

A2RB:

• Block AT₁ receptors

Mooney 2016

Further Reading:

Click to Open CICMWrecks Table: ACE-inhibitors and ARBs

Answer by Mooney