What Are ACE Inhibitors?

ACE inhibitors block the enzyme that converts angiotensin I to angiotensin II, reducing blood vessel constriction and lowering blood pressure. They are a first-line treatment for hypertension, heart failure, and diabetic kidney disease.

Mechanism

Block angiotensin-converting enzyme (ACE), preventing angiotensin I from becoming angiotensin II — a potent vasoconstrictor — and reducing aldosterone secretion.

Common Uses

Hypertension, heart failure with reduced ejection fraction, post-MI cardioprotection, diabetic nephropathy, chronic kidney disease with proteinuria.

Key Risks

Dry persistent cough (affects 10–15%), hyperkalemia, acute kidney injury (especially with NSAIDs or diuretics), angioedema (rare but serious), contraindicated in pregnancy.

Examples

Lisinopril (Prinivil, Zestril), enalapril (Vasotec), ramipril (Altace), benazepril (Lotensin), captopril.

How ACE Inhibitors Work

The renin-angiotensin-aldosterone system (RAAS) is a hormonal cascade that regulates blood pressure and fluid balance. When blood pressure drops, the kidneys release renin, which cleaves angiotensinogen into angiotensin I. Angiotensin-converting enzyme (ACE) — found mainly in the lungs — then converts angiotensin I into angiotensin II.

Angiotensin II is a powerful vasoconstrictor that narrows blood vessels and triggers the adrenal glands to release aldosterone, a hormone that causes the kidneys to retain sodium and water. The combined effect raises blood pressure significantly. ACE inhibitors block this conversion step, lowering angiotensin II levels, dilating blood vessels, and reducing aldosterone-driven fluid retention.

ACE also breaks down bradykinin, a vasodilator peptide. By inhibiting ACE, bradykinin accumulates — contributing to vasodilation but also to the class's hallmark side effect: a dry, persistent cough (from bradykinin accumulation in the airways). This cough affects roughly 10–15% of patients and is a leading reason for switching to an ARB, which achieves similar blood pressure control through a different mechanism without the cough.

Drugs in This Class

Lisinopril

Prinivil, Zestril

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Common Side Effects Across the Class

Dry persistent cough (most common)

Dizziness (especially first dose)

Elevated potassium (hyperkalemia)

Low blood pressure (hypotension)

Fatigue

Headache

Taste changes (metallic, rare)

Angioedema (rare but emergent)

Important Interactions & Warnings

Pregnancy — Contraindicated — ACE inhibitors cause severe fetal harm including kidney dysgenesis, oligohydramnios, and death. Discontinue immediately upon confirmed pregnancy and switch to a safe alternative.
Potassium-sparing diuretics and potassium supplements — ACE inhibitors reduce aldosterone, increasing potassium retention. Combining with spironolactone, amiloride, or potassium supplements can lead to dangerous hyperkalemia (high potassium), causing fatal cardiac arrhythmias.
NSAIDs — Reduce the antihypertensive effect of ACE inhibitors and, in combination, significantly increase the risk of acute kidney injury — a particularly dangerous triple combination when a diuretic is also present ("triple whammy").
Angioedema history — Patients with a history of ACE inhibitor-induced angioedema should never receive another ACE inhibitor; switch to an ARB. Angioedema involving the throat or tongue requires emergency care.
Concurrent ARB use — Combining an ACE inhibitor with an ARB provides no additional cardiovascular benefit and substantially increases the risk of kidney injury and hyperkalemia. This combination is generally avoided.

Frequently Asked Questions

Why do ACE inhibitors cause a cough?

ACE breaks down a peptide called bradykinin. When ACE is inhibited, bradykinin accumulates in the airways, where it stimulates cough receptors. This produces the characteristic dry, tickling cough that affects 10–15% of patients (more common in women and in people of East Asian descent). The cough resolves within weeks of stopping the ACE inhibitor. Switching to an ARB eliminates the cough because ARBs do not affect bradykinin metabolism.

Are ACE inhibitors and ARBs interchangeable?

They have similar blood pressure-lowering effects and both protect kidney function in diabetic nephropathy, but they are not identical. ACE inhibitors also increase bradykinin (causing cough and contributing to additional vasodilation), while ARBs selectively block angiotensin II receptors without affecting bradykinin. ARBs are generally the preferred switch for patients who cannot tolerate ACE inhibitor cough.

Do ACE inhibitors protect the kidneys?

Yes — in diabetic kidney disease and other forms of proteinuric chronic kidney disease, ACE inhibitors reduce pressure inside the kidney's filtering units (glomeruli) and decrease protein loss in the urine. This slows the progression of kidney disease beyond what blood pressure reduction alone would achieve. They are often continued even when kidney function is mildly impaired, though potassium and creatinine must be monitored.

What is angioedema and how serious is it?

Angioedema is a rapid, deep swelling of the skin or mucous membranes, often affecting the lips, tongue, throat, or face. ACE inhibitor-induced angioedema occurs in less than 1% of users but can be life-threatening if the airway is involved. It can appear at any point during therapy — even after years of use. Any swelling of the face, lips, or throat while on an ACE inhibitor requires immediate medical evaluation. Call 911 if breathing is affected.