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 respons es found in the myocardium in response to effector hormones of the ren in-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 m icroscopic scarring; b) chronic elevations in plasma aldosterone (ALDO ), relative to Na+ intake, are associated with a perivascular and inte rstitial fibrosis of the coronary and systemic circulations and are al so seen in response to chronic administration of the mineralocorticoid hormone deoxycorticosterone (DOC); and c) chronic mineralocorticoid e xcess, due to ALDO or DOC, is associated with enhanced urinary K+ excr etion, cardiac myocyte necrosis and scarring. Pharmacologic agents whi ch interfere with these effector hormones (e.g., ACE inhibition and AL DO receptor antagonism) protect the myocardium against this pathologic structural remodeling created by the reactive and replacement (repara tive) fibrosis. Evidence is also presented to indicate that chronic AC E inhibition is associated with a regression in reactive myocardial fi brosis. Based on these experimental findings we would suggest that cli nical trials are indicated to address the prevention and regression of myocardial fibrosis - an important determinant of pathologic structur al remodeling and abnormal myocardial stiffness.