🩺 Mechanism of Action: Renin-Angiotensin-Aldosterone System (RAAS) Inhibitors
The Renin-Angiotensin-Aldosterone System (RAAS) is a hormonal cascade critical for regulating blood pressure, fluid balance, and electrolyte homeostasis. The system is activated when there is decreased perfusion to the kidneys, low sodium levels, or low blood pressure. This triggers the release of renin from the juxtaglomerular cells in the renal corpuscle.
Renin catalyzes the conversion of angiotensinogen (from the liver) to angiotensin I, which is then converted into angiotensin II by the angiotensin-converting enzyme (ACE) primarily in the lungs. Angiotensin II is a potent vasoconstrictor and also stimulates aldosterone release from the adrenal cortex.
💊 Pharmacological Inhibition of RAAS
RAAS inhibitors disrupt this sequence at multiple points to treat hypertension, heart failure, and chronic kidney disease. Here are the main classes:
| Drug Class | Target Action Site | Effect on RAAS Cascade |
|---|---|---|
| ACE Inhibitors (e.g., enalapril) | Inhibit ACE | ↓ Angiotensin II, ↑ Bradykinin, ↓ BP |
| ARBs (e.g., losartan) | Block Angiotensin II receptors | ↓ Vasoconstriction, ↓ Aldosterone, ↓ BP |
| Aliskiren | Direct renin inhibitor | ↓ Angiotensin I & II, ↓ Aldosterone |
| Aldosterone Antagonists (e.g., spironolactone) | Block aldosterone receptors | ↓ Na⁺ retention, ↑ K⁺, ↓ BP |
🩻 Clinical Relevance (USMLE/Step 1 Focus)
ACE inhibitors increase bradykinin, which explains their side effects like dry cough and angioedema.
ARBs do not increase bradykinin levels and are often used as alternatives in ACE inhibitor-intolerant patients.
Aldosterone antagonists are potassium-sparing and are essential in the management of heart failure with reduced ejection fraction.
Aliskiren is less commonly used but directly targets the renin step.
📈 Visual Summary
The diagram above provides a step-by-step overview of how each drug affects the RAAS cascade—an essential concept for mastering cardiorenal pharmacology on exams like the USMLE Step 1 or COMLEX.
🧪 Memorization Tip
“RAAS gets BLOCKED at every step — Renin (Aliskiren), ACE (ACE inhibitors), Angiotensin II receptor (ARBs), and Aldosterone receptor (Spironolactone).”
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