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Actions of angiotensin II on the heart

Timothy W Smith, MD, PhD
James P Morgan, MD, PhD
Section Editor
Wilson S Colucci, MD
Deputy Editor
Susan B Yeon, MD, JD, FACC


The renin-angiotensin system is a classic endocrine system, and angiotensin II is the primary effector hormone that is secreted in response to physiologic stimuli. However, there is now general agreement that there are complete local renin-angiotensin systems existing entirely within organs or tissues, which function in an autocrine or paracrine fashion [1]. Aldosterone and angiotensin converting enzyme (ACE) are also produced by the failing heart, in proportion to the severity of heart failure [2,3]. (See "Pathophysiology of heart failure: Neurohumoral adaptations".)

Synthesis of angiotensin II — Angiotensin II is an oligopeptide of eight amino acids, formed from its original precursor, angiotensinogen, by a series of two enzymatic cleavages.

Angiotensinogen is released into the circulation by the liver. Renin, produced by the kidney, in response to glomerular hypoperfusion, catalyzes cleavage of angiotensinogen to angiotensin I, a decapeptide.

Angiotensin I is in turn cleaved by ACE to produce the octapeptide angiotensin II. The concentration of ACE is highest in the lung and it had been thought that most angiotensin II formation occurred in the pulmonary circulation. It is now clear, however, that ACE is produced in the vascular endothelium of many tissues; thus, angiotensin II can be synthesized at a variety of sites, including the kidney, vascular endothelium, adrenal gland, and brain. In addition, alternative enzymatic pathways not involving ACE may contribute to angiotensin II production. Human heart chymase may be one such enzyme but its clinical significance remains uncertain. (See 'Alternate pathways of angiotensin II production' below.)

Angiotensin II binds to its specific receptors and exerts its effects in the brain, kidney, adrenal, vascular wall, and the heart.

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Literature review current through: Nov 2017. | This topic last updated: Nov 02, 2015.
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