 2. Myocardial and vascular hypertrophy and fibrosis: Aldosterone appears to cause myocardial and vascular injury independently of effects on blood pressure. Chronic aldosterone infusion and sodium loading resulted in myocardial fibrosis and ventricular hypertrophy in rats. Treatment with aldosterone receptor antagonists prevented aortic and myocardial fibrosis in rat models of hypertension even in the absence of blood pressure lowering. In addition, in aldosterone treated stroke-prone hypertensive rats, spironolactone exerted a powerful protective effect against the development of nephrosclerotic and cerebrovascular lesions. The mechanisms of action of aldosterone may include upregulation of AT1 receptors, direct effects on fibroblast collagen synthesis and possibly decreased matrix metallo-proteinase secretion. In humans, aldosterone concentrations have been correlated with mortality in chronic heart failure, with the severity of LVH in non-diabetic renal failure and hypertension and negatively with carotid artery compliance in hypertension. When added to ACE inhibitors, treatment with aldosterone receptor antagonists further reduces LVH in both hypertension and heart failure. Myocardial collagen turnover a marker for fibrosis was significantly reduced by spironolactone in the RALES study and the fall in the marker of this index was related to the mortality benefit. 