Aldosterone: A Mediator of Myocardial Necrosis and Renal Arteriopathy*

TLDR

The study aimed to determine whether aldosterone mediates cardiovascular damage. The authors performed aldosterone ablation/replacement experiments in a rat model of cardiac injury. Aldosterone ablation or eplerenone markedly reduced cardiac and renal damage, while aldosterone infusion restored it, indicating aldosterone is a critical mediator of L‑NAME/angiotensin II–induced vascular damage independent of blood pressure.

Abstract

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 Nω-nitro-l-arginine methyl ester (L-NAME; nitric oxide synthesis inhibitor) to male rats drinking 1% saline caused hypertension, severe biventricular myocardial necrosis, proteinuria, and fibrinoid necrosis of renal and cardiac vessels. Removal of aldosterone by adrenalectomy or through administration of the selective aldosterone antagonist eplerenone markedly reduced the cardiac and renal damage without significantly altering blood pressure. Aldosterone infusion in adrenalectomized, glucocorticoid-replaced L-NAME/angiotensin II-treated animals restored damage. Thus, we identified aldosterone as a critical mediator of L-NAME/angiotensine II induced vascular damage through mechanisms apparently independent of its effects on systolic blood pressure.