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To examine the inter-relationship between effector hormones of the renin-angiotensin-aldosterone system and fibrosis, a determinant of abnormal myocardial stiffness, and to determine whether pharmacological interference with these hormones can prevent or regress this pathological structural remodeling.Two morphological expressions of myocardial fibrosis are evident, a perivascular and interstitial fibrosis, not related to cardiac myocyte necrosis, and microscopic scarring that replaces lost myocytes. The former, a reactive fibrosis, is related to elevations in circulating mineralocorticoids (aidosterone or deoxycorticosterone) with increased dietary sodium, and not to arterial hypertension or ventricular loading. Scarring follows the cytotoxicity associated with elevated plasma angiotensin II levels and the increased K+ excretion that accompanies chronic mineralocorticoid excess.Given the association of these hormones with fibrosis, the concept of cardioprotection was evaluated in various prevention trials. Reactive fibrosis was prevented in unilateral renal ischaemia by angiotensin converting enzyme (ACE) inhibition with captopril and in either primary or secondary hyperaldosteronism by antagonism of the aidosterone receptor with spironolactone. Scarring (and cell loss) was prevented in renal ischemia by captopril and by K + -sparing diuretics (spironolactone, amiloride) in primary hyperaldosteronism. In treatment trials, where reactive fibrosis was established, lisinopril promoted regression of the fibrosis and therefore was cardioprotective.Myocardial fibrosis is related to chronic mineralocorticoid excess (with increased dietary sodium), angiotensin II and increased K+ excretion. Cardioprotective and cardioreparative strategies that respectively prevent or regress the development of fibrous tissue have been demonstrated in experimental models and now merit clinical evaluation.