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Angiotensin converting enzyme inhibitors and receptor blockers in heart failure: Mechanisms of action

Wilson S Colucci, MD
Section Editor
Stephen S Gottlieb, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC


Angiotensin converting enzyme (ACE) inhibition is a key component of the medical therapy of heart failure (HF) with systolic dysfunction [1]. Angiotensin II receptor blockers (ARBs) are an alternative to ACE inhibitors in patients who cannot tolerate these drugs. (See "Overview of the therapy of heart failure with reduced ejection fraction".)

The mechanisms of action of ACE inhibitors and angiotensin II receptor blockers (ARBs) in patients with HF will be reviewed here. A review of the clinical data supporting the use of ACE inhibitors in patients with HF and the initial clinical data on the ARBs are discussed separately. (See "ACE inhibitors in heart failure with reduced ejection fraction: Therapeutic use" and "Use of angiotensin II receptor blocker in heart failure with reduced ejection fraction".)


Despite years of use and strong data supporting their efficacy, the mechanism by which angiotensin converting enzyme (ACE) inhibitors act in heart failure (HF) is incompletely understood. The observation that other vasodilators do not improve survival (or do so to a lesser degree than ACE inhibitors) or may actually worsen cardiac function and/or clinical outcomes has led to the conclusion that ACE inhibitors work by a mechanism other than simply decreasing preload and afterload, or that detrimental effects due to vasodilation per se (eg, renin-angiotensin aldosterone system or sympathetic activation) are countered by other actions of the ACE inhibitors. (See "Overview of the therapy of heart failure with reduced ejection fraction".)

Intracardiac renin-angiotensin system — The observation that, in the failing human myocardium, there is a reduction in gene expression and selective downregulation of one subtype of the angiotensin II receptor (AT1) is compatible with enhanced local activity of angiotensin II [2,3]. (See "Actions of angiotensin II on the heart".) The reduction in AT1 receptor density paralleled the reduction in the density of ß1 receptors.

Increased local activity of angiotensin II may be due in part to enhanced ACE activity within the myocardium. An increase in ACE binding sites has been identified in the ventricular myocardium of patients with end-stage HF [4]. This was localized to both endothelial cells and myocytes in a pattern similar to the AT1 receptors.

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Literature review current through: Oct 2017. | This topic last updated: Dec 22, 2016.
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