Abstract-The renin-angiotensin-aldosterone system is involved in the arterial hypertension-associated cardiovascular remodeling. In this context, the development of cardiac fibrosis results from an imbalance between profibrotic and antifibrotic pathways, in which the role of aldosterone is yet not established. To determine the role of intracardiac aldosterone in the development of myocardial fibrosis during hypertension, we used a double transgenic model (AS-Ren) of cardiac hyperaldosteronism (AS) and systemic hypertension (Ren). The 9-month-old hypertensive mice had cardiac fibrosis, and hyperaldosteronism enhanced the fibrotic level. The mRNA levels of connective tissue growth factor and transforming growth factor-␤1 were similarly increased in Ren and AS-Ren mice compared with wild-type and AS mice, respectively. Hyperaldosteronism combined with hypertension favored the macrophage infiltration (CD68 ϩ cells) in heart, and enhanced the mRNA level of monocyte chemoattractant protein 1, osteopontin, and galectin 3. Interestingly, in AS-Ren mice the hypertension-induced increase in bone morphogenetic protein 4 mRNA and protein levels was significantly inhibited, and B-type natriuretic peptide expression was blunted. The mineralocorticoid receptor antagonist eplerenone restored B-type natriuretic peptide and bone morphogenetic protein 4 levels and decreased CD68 and galectin 3 levels in AS-Ren mice. Finally, when hypertension was induced by angiotensin II infusion in wild-type and AS mice, the mRNA profiles did not differ from those observed in Ren and AS-Ren mice, respectively. The aldosterone-induced inhibition of B-type natriuretic peptide and bone morphogenetic protein 4 expression was confirmed in vitro in neonatal mouse cardiomyocytes. Altogether, we demonstrate that, at the cardiac level, hyperaldosteronism worsens hypertension-induced fibrosis through 2 mineralocorticoid receptor-dependent mechanisms, activation of inflammation/galectin 3-induced fibrosis and inhibition of antifibrotic factors (B-type natriuretic peptide and bone morphogenetic protein 4). A rterial hypertension is known to induce cardiac remodeling, characterized by fibrosis, a risk factor for heart failure. Until now the hypertrophic, proinflammatory, and profibrotic actions of angiotensin II (Ang II) have been thought to be the major players in this cardiac remodeling. However, aldosterone concentrations have also been found to be inappropriately high in many hypertensive patients.1 Aldosterone regulates sodium and potassium homeostasis, thereby regulating blood volume and pressure, and both clinical and experimental studies have demonstrated additional roles for aldosterone in cardiac remodeling. For example, mineralocorticoid receptor (MR) antagonists have been demonstrated to prevent cardiac fibrosis in patients with heart failure.2 Recent studies have suggested that the profibrotic action of aldosterone involves an inflammatory step.3 Two main pathways have been shown to be involved in the development of this cardiac fibrosis. The tr...