Modifying influence of enalaprilat on mesangial cell DNA synthesis induced by hydrogen peroxide

Abstract

This study examined the effect of the angiotensin converting enzyme (ACE) inhibitor, enalaprilat, on mesangial cell (MC) DNA synthesis induced by H 2O 2, IL-6 and PDGF. MC were incubated with enalaprilat (2.5–100 μmol/l) alone and together with combinations of H 2O 2 (3 daily pulses of 10 −6 mol/l), IL-6 (5 ng/ml) and PDGF (10 ng/ml). DNA synthesis was assessed after 72 h using [ 3H]thymidine ( 3H-TdR) incorporation. Enalaprilat alone had no effect on MC DNA synthesis. Stimulation of MC by H 2O 2, PDGF and IL-6 alone resulted in increases in 3H-TdR of 4936.6 ± 1147.5, 5640.5 ± 1537.6 and 4413.5 ± 998.4 cpm, respectively ( P < 0.05 above control). Only 2.5 μmol/l enalaprilat effected a significant reduction in IL-6 and PDGF-induced DNA synthesis. Incubation of MC with H 2O 2 + PDGF or H 2O 2 + IL-6 resulted in increases of 3H-TdR of 6471.9 ± 1785.1 and 5507.2 ± 1270 cpm, respectively ( P < 0.05 above control). Addition of enalaprilat with either H 2O 2 + PDGF or H 2O 2 + IL-6 effected significant reductions in DNA synthesis over the range 2.5–100 μmol/l. These data demonstrate that ACE inhibitors modulate MC DNA synthesis induced by reactive oxygen species.