PHARMACOLOGICAL AGENTS INHIBIT RAT MESANGIAL CELL-PROLIFERATION AND COLLAGEN-SYNTHESIS

Prevention of the development of end-stage renal disease is one of the most promising areas of research in nephrology. Because mesangial cel l proliferation and extracellular matrix accumulation have been regard ed as antecedents of glomerulosclerosis, agents that can inhibit mesan gial cell proliferation may hare a potential to retard the progression of renal diseases. Therefore, we investigated several clinically avai lable agents that might affect mesangial cell proliferation and collag en synthesis in male Sprague-Dawley rats. Cell proliferation was measu red by the tetrazolium dye uptake method. Collagen synthesis was measu red by H-3-proline incorporation into pepsin-resistant, salt-precipita ted collagen. Intracellular cAMP levels were measured by enzyme immuno assay. Our results showed that hydralazine (82% inhibition at 10 mu g/ mL), ticlopidine (61% inhibition at 30 mu g/mL), aminophylline (66% in hibition at 200 mu g/mL), and nicametate (91% inhibition at 1 mg mL) i nhibited serum-stimulated rat mesangial cell (RMC) growth in a dose-de pendent manner. Ticlopidine (43% inhibition at 30 mg/mL), aminophyllin e (52% inhibition at 200 mg/mL), and nicametate (35% inhibition at 1 m g/mL) inhibited collagen synthesis in confluent RMCs. Aminophylline ma y act through increasing intracellular cAMP levels (9.7 +/- 0.7 pmol/m g protein at 200 mu g/mL of aminophylline vs 4.2 +/- 0.6 pmol/mg prote in at control). These data suggest that aminophylline, ticlopidine, hy dralazine, and nicametate can inhibit RMC proliferation and collagen s ynthesis.