Aldosterone contributes to cardiac failure, which is associated with induction of inflammatory mediators. Moreover, aldosterone was shown to induce a vascular inflammatory phenotype in the rat heart. Using Western blotting and/or real-time RT-PCR, we examined the effect of aldosterone on the expression of the proinflammatory molecules, cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6), in neonatal rat ventricular cardiac myocytes and fibroblasts as well as in adult cardiomyocytes after myocardial infarction. In cardiomyocytes, aldosterone induced COX-2 but not IL-6 expression. Following 4-18 h of stimulation with 1 µM aldosterone, a significant increase in COX-2 protein expression was observed, preceded by an increase of COX-2 mRNA levels. After 18 h treatment, 100 nM and 1 µM aldosterone increased COX-2 protein amount by 2 and 4-fold, respectively. Consistently, aldosterone increased by 2.5-fold prostaglandin E₂ (PGE₂) secretion in cardiomyocytes. In cardiac fibroblasts, aldosterone did neither increase COX-2 nor IL-6 mRNA expression. Interestingly, PGE₂ (100 nM) strongly induced both proinflammatory molecules in fibroblasts and cardiomyocytes. Our results indicate that aldosterone directly induces COX-2 expression in cardiomyocytes and suggest that the subsequent increase in prostaglandin secretion may act in an autocrine and/or paracrine manner inducing in turn COX-2 and IL-6 expression. In vivo, myocardial infarction strongly increased both COX-2 and IL-6 expression in ventricular cardiomyocytes. Administration of the aldosterone antagonist RU28318 completely prevented COX-2 induction by infarction and partially inhibited the increase in IL-6 mRNA. These data suggest that following myocardial infarction, mineralocorticoid receptor activity is responsible for COX-2 induction and indirectly participate to IL-6 expression in cardiomyocytes.