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Mnemonic

Renin-Angiotensin-Aldosterone System

A memory aid for the steps of the renin-angiotensin-aldosterone cascade.

Physiology Cardiology Pharmacology Cardiovascular Hypertension and Lipids Cardiovascular Pharmacology
Expansion

Renin, angiotensinogen, angiotensin I, ACE, angiotensin II, aldosterone

Mnemonic

“Renin, angiotensinogen, ACE, aldosterone”, a chain in which each step has a drug:

  • Renin from the juxtaglomerular cells, released by low renal perfusion, low sodium at the macula densa, and sympathetic (beta-1) stimulation. Blocked by aliskiren
  • Angiotensinogen from the liver is cleaved to angiotensin I
  • ACE, mostly in the lung, converts it to angiotensin II. Blocked by ACE inhibitors
  • Angiotensin II acts on AT1 receptors: vasoconstriction, thirst, ADH release, proximal sodium reabsorption, and efferent arteriolar constriction to preserve GFR. Blocked by ARBs
  • Aldosterone from the zona glomerulosa: sodium in, potassium and hydrogen out at the collecting duct. Blocked by spironolactone

“Beta blockers cut it off at the top, spironolactone at the bottom.”

ACE also degrades bradykinin, which is why ACE inhibitors cause cough and angioedema while ARBs do not.

Angiotensin II constricts the efferent arteriole, which is why ACE inhibitors cause a rise in creatinine on starting, and why that rise is expected and acceptable up to about 30 per cent.

Expansion

  1. Renin released from juxtaglomerular cells
  2. Cleaves angiotensinogen (from the liver) to angiotensin I
  3. Angiotensin converting enzyme, mainly in pulmonary endothelium, converts it to angiotensin II
  4. Angiotensin II stimulates aldosterone release from the zona glomerulosa

Triggers for renin release

  • Reduced renal perfusion pressure, sensed by the afferent arteriole
  • Reduced sodium delivery to the macula densa
  • Sympathetic stimulation through beta-1 receptors

Actions of angiotensin II: potent vasoconstriction, aldosterone and antidiuretic hormone release, thirst, sympathetic facilitation, and preferential constriction of the efferent arteriole to preserve glomerular filtration.

Aldosterone promotes sodium and water retention with potassium and hydrogen ion loss in the distal nephron.

Drug targets: beta blockers reduce renin release, ACE inhibitors block conversion, angiotensin receptor blockers block the receptor, and spironolactone blocks aldosterone.