© 1999 American Heart Association, Inc.
Review |
The Cardiac Renin-Angiotensin System
Conceptual, or a Regulator of Cardiac Function?
From The Cardiovascular Research Institute, Division of Molecular Cardiology, The Texas A&M University System Health Science Center, Temple, Tex.
Correspondence to David E. Dostal, PhD, The Cardiovascular Research Institute, Division of Molecular Cardiology, The Texas A&M University System HSC, 1901 S 1st St, Bldg 162, Temple, TX 76504. E-mail ddostal{at}medicine.tamu.edu
Abstract—Angiotensin II, the effector peptide of the renin-angiotensin system, regulates cellular growth in response to developmental, physiological, and pathological processes. The identification of renin-angiotensin system components and angiotensin II receptors in cardiac tissue suggests the existence of an autocrine/paracrine system that has effects independent of angiotensin II derived from the circulatory system. To be functional, a local renin-angiotensin system should produce sufficient amounts of the autocrine and/or paracrine factor to elicit biological responses, contain the final effector (angiotensin II receptor), and respond to humoral, neural, and/or mechanical stimuli. In this review, we discuss evidence for a functional cardiac renin-angiotensin system.
Key Words: renin • angiotensinogen • angiotensin II • cardiac myocyte • cardiac fibroblast
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|
|
|
|
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|
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|
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|
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|
|
|
|
|
|
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|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
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|
|
|
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