title: 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 H2O2, IL-6 and PDGF. MC were incubated with enalaprilat (2.5-100 mumol/l) alone and together with combinations of H2O2 (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 H2O2, 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 mumol/l enalaprilat effected a significant reduction in IL-6 and PDGF-induced DNA synthesis. Incubation of MC with H2O2 + PDGF or H2O2 + 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 H2O2 + PDGF or H2O2 + IL-6 effected significant reductions in DNA synthesis over the range 2.5-100 mumol/l. These data demonstrate that ACE inhibitors modulate MC DNA synthesis induced by reactive oxygen species.
authors.affiliation: Renal and Clinical Biochemistry Research Laboratory, School of postgraduate Medicine, University of Keele, North Staffordshire Hospital Centre, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: D'Souza
authors.forename: H M
authors.initials: HM
authors.lastname: Phillips
authors.forename: R C
authors.initials: RC
authors.lastname: Strange
authors.forename: G M
authors.initials: GM
authors.lastname: Aber
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival; D004261:DNA Replication / Q000187:drug effects*; D015773:Enalaprilat / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015850:Interleukin-6; D010982:Platelet-Derived Growth Factor; D006861:Hydrogen Peroxide; D015773:Enalaprilat