MODIFYING INFLUENCE OF ENALAPRILAT ON MESANGIAL CELL-DNA SYNTHESIS INDUCED BY HYDROGEN-PEROXIDE

This study examined the effect of the angiotensin converting enzyme (A CE) inhibitor, enalaprilat, on mesangial cell (MC) DNA synthesis induc ed by H2O2, IL-6 and PDGF. MC were incubated with enalaprilat (215-100 mu mol/l) alone and together with combinations of H2O2 (3 daily pulse s of 10(-6) mol/l), IL-6 (5 ng/ml) and PDGF (10 ng/ml). DNA synthesis was assessed after 72 h using [H-3]thymidine (H-3-TdR) incorporation. Enalaprilat alone had no effect on MC DNA. synthesis. Stimulation of M C by H2O2, PDGF and IL-6 alone resulted in increases in H-3-TdR of 493 6.6 +/- 1147.5, 5640.5 +/- 1537.6 and 4413.5 +/- 998.4 cpm, respective ly (P < 0.05 above control). Only 2.5 mu mol/l enalaprilat effected a significant reduction in IL-6 and PDGF-induced DNA synthesis. Incubati on of MC with H2O2 + PDGF or H2O2 + IL-6 resulted in increases of H-3- TdR of 6471.9 +/- 1785.1 and 5507.2 +/- 1270 cpm, respectively (P < 0. 05 above control). Addition of enalaprilat with either H2O2 + PDGF or H2O2+ IL-6 effected significant reductions in DNA synthesis over the r ange 2.5-100 mu mol/l. These data demonstrate that ACE inhibitors modu late MC DNA synthesis induced by reactive oxygen species. (C) 1997 Els evier Science B.V.