Does aldosterone-induced cardiac fibrosis involve direct effects on cardiac fibroblasts?
To investigate the hypothesis that aldosterone plays a role in the development of fibrosis, cultured fibroblasts from adult rat heart have been examined for their expression of aldosterone receptors and the effects of aldosterone on collagen synthesis. Binding assays with both 3H-aldosterone and 3H-RU26752 in intact cardiac fibroblasts and cytosolic extracts from cardiac fibroblasts failed to reveal expression of aldosterone receptors. However, using the method of reverse transcription-polymerase chain reaction, we could demonstrate the expression of mRNA for the mineralocorticoid receptor in both cardiac fibroblasts and neonatal rat cardiomyocytes. Functional studies investigating the effect of aldosterone on collagen synthesis (3H-proline incorporation into collagenous protein) revealed that aldosterone does not stimulate collagen synthesis in cardiac fibroblasts at concentrations (10(-8) to 10(-9) M) observed in primary or secondary hyperaldosteronism. At higher concentrations (10(-