Angiotensin converting enzyme function

ACE - The Lung's Workhorse

• Primary Function: Converts Angiotensin I → Angiotensin II.
• Location: Primarily on the surface of pulmonary (lung) and renal endothelial cells.
• Secondary Function: Inactivates bradykinin (a vasodilator).
  • This breakdown is key to understanding ACE inhibitor side effects (e.g., dry cough, angioedema) which result from ↑ bradykinin.

⭐ ACE's dual action is a high-yield concept: it simultaneously generates a potent vasoconstrictor (Angiotensin II) while degrading a vasodilator (bradykinin), robustly increasing blood pressure.

ACE's Two-Step - Make & Break

• Dual Function: ACE is a peptidase primarily located on the surface of pulmonary and renal endothelial cells. It plays two major roles in blood pressure regulation.

• Make (Activation): Converts inactive Angiotensin I to the highly active Angiotensin II.

  • Angiotensin II effects: vasoconstriction, aldosterone release (Na⁺/H₂O retention), ADH release.

• Break (Inactivation): Degrades bradykinin, a potent vasodilator.

  • Bradykinin also mediates inflammation, pain, and the cough reflex.

⭐ High-Yield: ACE inhibitors (e.g., lisinopril) cause accumulation of bradykinin. This contributes to their therapeutic effect but also causes the classic side effects of dry cough and, rarely, angioedema.

Inhibiting ACE - The '-prils' Story

• Dual Function of ACE:

  • Converts Angiotensin I → Angiotensin II (potent vasoconstrictor).
  • Breaks down Bradykinin (a vasodilator).

• Mechanism of ACE Inhibitors (-pril drugs: Lisinopril, Captopril):

  • Block the conversion of Angiotensin I to Angiotensin II.
  • Result: ↓ Angiotensin II → Vasodilation (↓ TPR) & ↓ Aldosterone secretion.
  • Prevents Bradykinin breakdown → ↑ Bradykinin levels.

• Key Side Effects & Causes:

  • Dry, non-productive cough: Due to ↑ Bradykinin in the lungs.
  • Angioedema: Swelling of face/airways; also from ↑ Bradykinin.
  • Hyperkalemia: Due to ↓ Aldosterone → ↓ K+ excretion.
  • Hypotension: Especially first-dose effect.

⭐ Contraindications: ACE inhibitors are teratogenic and absolutely contraindicated in pregnancy. Also contraindicated in patients with bilateral renal artery stenosis.

📌 Mnemonic (CAPTOPRIL):

• Cough
• Angioedema/ Agranulocytosis
• Proteinuria/ Potassium excess
• Taste changes
• Orthostatic hypotension
• Pregnancy (contraindicated)
• Renal artery stenosis (contraindicated) / Rash
• Increased renin
• Lower GFR

High‑Yield Points - ⚡ Biggest Takeaways

• ACE converts angiotensin I to angiotensin II (a potent vasoconstrictor), primarily in the lungs.
• It is a key drug target for controlling hypertension.
• ACE also inactivates bradykinin, a potent vasodilator.
• Inhibition of bradykinin breakdown by ACE inhibitors is responsible for side effects like dry cough and angioedema.
• The enzyme is a dipeptidyl carboxypeptidase found on the surface of endothelial cells.