Myocardial fibrosis: role of angiotensin II and aldosterone.
In this report we review the replacement (i.e., scarring) and reactive (i.e., perivascular and interstitial fibrosis) fibrous tissue responses found in the myocardium in response to effector hormones of the renin-angiotensin-aldosterone system. Experimental data are presented to indicate: a) endogenous or exogenous elevations in plasma angiotensin II are associated with acute cardiac myocyte necrosis and subsequent microscopic scarring; b) chronic elevations in plasma aldosterone (ALDO), relative to Na+ intake, are associated with a perivascular and interstitial fibrosis of the coronary and systemic circulations and are also seen in response to chronic administration of the mineralocorticoid hormone deoxycorticosterone (DOC); and c) chronic mineralocorticoid excess, due to ALDO or DOC, is associated with enhanced urinary K+ excretion, cardiac myocyte necrosis and scarring. Pharmacologic agents which interfere with these effector hormones (e.g., ACE inhibition and ALDO receptor antagonism) protect the myocardium against this pathologic structural remodeling created by the reactive and replacement (reparative) fibrosis. Evidence is also presented to indicate that chronic ACE inhibition is associated with a regression in reactive myocardial fibrosis. Based on these experimental findings we would suggest that clinical trials are indicated to address the prevention and regression of myocardial fibrosis--an important determinant of pathologic structural remodeling and abnormal myocardial stiffness.
Department of Internal Medicine, University of Missouri-Columbia.
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Weber
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Brilla
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Campbell
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Guarda
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Zhou
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Sriram
D000450:Aldosterone / Q000009:adverse effects*; D000804:Angiotensin II / Q000009:adverse effects*; D000818:Animals; D004151:Dipeptides / Q000494:pharmacology; D004719:Endomyocardial Fibrosis / Q000139:chemically induced / Q000517:prevention & control*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D017706:Lisinopril; D000451:Mineralocorticoid Receptor Antagonists; D014945:Wound Healing
D004151:Dipeptides; D000451:Mineralocorticoid Receptor Antagonists; D000804:Angiotensin II; D000450:Aldosterone; D017706:Lisinopril