Aldosterone: A mediator of myocardial necrosis and renal arteriopathy

To determine the role of aldosterone in mediating cardiovascular damage, we performed ablation/replacement experiments with aldosterone in a rat model of cardiac injury, Administration of angiotensin II and N-omega-nitro-L-ar ginine methyl ester (L-NAME; nitric oxide synthesis inhibitor) to male rats drinking 1% saline caused hypertension, severe biventricular myocardial ne crosis, proteinuria, and fibrinoid necrosis of renal and cardiac vessels. R emoval of aldosterone by adrenalectomy or through administration of the sel ective aldosterone antagonist eplerenone markedly reduced the cardiac and r enal damage without significantly altering blood pressure. Aldosterone infu sion in adrenalectomized, glucocorticoid-replaced L-NAME/angiotensin II-tre ated animals restored damage. Thus, we identified aldosterone as a critical mediator of L-NAME/angiotensine II induced vascular damage through mechani sms apparently independent of its effects on systolic blood pressure.