title: Antioxidants modulate the antiproliferative effects of nitric oxide on vascular smooth muscle cells and adventitial fibroblasts by regulating oxidative stress.
abstract: BACKGROUND
  S-nitrosothiols (SNO) release nitric oxide (NO) through interaction with ascorbic acid (AA). However, little is known about their combined effect in the vasculature. The aim of this study was to investigate the effect of AA on SNO-mediated NO release, proliferation, cell cycle progression, cell death, and oxidative stress in vascular cells.
  
  
  METHODS
  Vascular smooth muscle cells and adventitial fibroblasts harvested from the aortae of Sprague-Dawley rats were treated with AA, ± S-nitrosoglutathione (GSNO), or ± diethylenetriamine NONOate (DETA/NO). NO release, proliferation, cell cycle progression, cell death, and oxidative stress were determined by the Griess reaction, [(3)H]-thymidine incorporation, flow cytometry, trypan blue exclusion, and 5-(and-6)chloromethyl-2',7'dichlorodihydrofluorescein staining, respectively.
  
  
  RESULTS
  AA increased NO release from GSNO 3-fold (P < .001). GSNO and DETA/NO significantly decreased proliferation, but AA abrogated this effect (P < .05). Mirroring the proliferation data, changes in cell cycle progression induced by GSNO and DETA/NO were reversed by the addition of AA. GSNO- and DETA/NO-mediated increases in oxidative stress were significantly decreased by the addition of AA (P < .001).
  
  
  CONCLUSIONS
  Despite causing increased NO release from GSNO, AA reduced the antiproliferative and cell cycle effects of GSNO and DETA/NO through the modulation of oxidative stress.
authors.affiliation: Division of Vascular Surgery, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Gregory
authors.forename: Ashley K
authors.initials: AK
authors.lastname: Vavra
authors.forename: Edward S
authors.initials: ES
authors.lastname: Moreira
authors.forename: George E
authors.initials: GE
authors.lastname: Havelka
authors.forename: Qun
authors.initials: Q
authors.lastname: Jiang
authors.forename: Vanessa R
authors.initials: VR
authors.lastname: Lee
authors.forename: Robert
authors.initials: R
authors.lastname: Van Lith
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Ameer
authors.forename: Melina R
authors.initials: MR
authors.lastname: Kibbe
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003238:Connective Tissue; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D026422:S-Nitrosoglutathione / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D017382:Reactive Oxygen Species; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D001205:Ascorbic Acid