Document Detail

Antioxidants modulate the antiproliferative effects of nitric oxide on vascular smooth muscle cells and adventitial fibroblasts by regulating oxidative stress.
MedLine Citation:
PMID:  21944289     Owner:  NLM     Status:  MEDLINE    
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.
Elaine K Gregory; Ashley K Vavra; Edward S Moreira; George E Havelka; Qun Jiang; Vanessa R Lee; Robert Van Lith; Guillermo A Ameer; Melina R Kibbe
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-23
Journal Detail:
Title:  American journal of surgery     Volume:  202     ISSN:  1879-1883     ISO Abbreviation:  Am. J. Surg.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-21     Completed Date:  2011-12-29     Revised Date:  2014-09-05    
Medline Journal Info:
Nlm Unique ID:  0370473     Medline TA:  Am J Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  536-40     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Antioxidants / pharmacology*
Ascorbic Acid / pharmacology
Cell Cycle / drug effects
Cell Proliferation / drug effects
Cells, Cultured
Connective Tissue
Fibroblasts / drug effects*,  physiology
Muscle, Smooth, Vascular / cytology
Myocytes, Smooth Muscle / drug effects*,  physiology
Nitric Oxide / metabolism*
Nitric Oxide Donors / pharmacology
Nitroso Compounds / pharmacology
Oxidative Stress / drug effects*
Rats, Sprague-Dawley
Reactive Oxygen Species
S-Nitrosoglutathione / pharmacology
Grant Support
K08 HL084203/HL/NHLBI NIH HHS; K08 HL084203-05/HL/NHLBI NIH HHS; K08HL084203/HL/NHLBI NIH HHS; T32 HL094293-01/HL/NHLBI NIH HHS; T32 HL094293-03/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Antioxidants; 0/Nitric Oxide Donors; 0/Nitroso Compounds; 0/Reactive Oxygen Species; 146724-94-9/2,2'-(hydroxynitrosohydrazono)bis-ethanamine; 31C4KY9ESH/Nitric Oxide; 57564-91-7/S-Nitrosoglutathione; PQ6CK8PD0R/Ascorbic Acid

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