Previous studies have shown an association between plasma prorenin level, hypertension and cardiac damage. To investigate whether prorenin is able to modulate cardiac functions, we over expressed the rat preprorenin gene in H9c2 cells under control of the CMV promotor using the pIRES vector. We measured the RAS components, the metabolic activity (protein content, LDH activity and glucose consumption) and the cell death (LDH release, ATP content) in H9c2, H9c2 pIRES and H9c2 preprorenin-producing cells (H9c2 PP). H9c2 PP cells contained 4100 fold more prorenin (p<0.001), 1000 fold more renin (p>0.001) than H9c2 and H9c2 pIRES cells. Within 24h H9c2 PP cells released 15000 fold more prorenin (p<0.001), 40 fold more renin (0.001) and 3 fold more angiotensinogen (p<0.05) into the medium. Ang I and Ang II levels in the cells and the medium were not different between the cell lines. H9c2 PP cells showed a 2 fold decreased growth rate (p>0.01) and a 2 fold enhanced protein content (p<0.05). Glucose consumption and LDH activity were increased 3 fold and 4 fold (p<0.01) compared to control lines. Cell death of H9c2 PP cells occured accelerated. Beginning at day 6 cells died as seen in the severe decrease of ATP content and LDH release. In conclusion, prorenin or possibly renin is capable to induce protein synthese and to enhance metabolic activity. The observed reduction of growth may be due to the accelerated prorenin-induced cell death.