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Objective To investigate the effects of glucose and aldosterone on the proliferation of rat cardiac fibroblasts. Methods The neonatal SD rat cardiac fibroblasts (Cfs) were separated by the differential attachment technique. Cfs were incubated in different D-glucose concentrations for 24 hours, with or without aldosterone. DNA synthesis and metabolic activity of the Cfs were measured simultaneously with Brdu incorporation and WST-1 ELISA, respectively. Results Glucose at high concentrations (15 and 25 mmol/L) significantly increased the proliferation of Cfs, compared with glucose at low concentration (5.6 mmol/L, .PO.01), while no difference was shown on Cfs proliferation between the two high glucose concentration groups. Addition of aldosterone (10-7 mmol/L) to low-glucose media resulted in significant proliferation compared with those without aldosterone (WST-1, P0.05). Further analysis suggested that aldosterone have significant interaction on Cfs DNA synthesis (P=0.012). Conclusions Both glucose and aldosterone could stimulate the proliferation of cultured Cfs. In high glucose concentration, the stimulatory effect for Cfs proliferation may be masked.