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.
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: Donald Lloyd-Jones; Robert J Adams; Todd M Brown; Mercedes Carnethon; Shifan Dai; Giovanni De Simone; T Bruce Ferguson; Earl Ford; Karen Furie; Cathleen Gillespie; Alan Go; Kurt Greenlund; Nancy Haase; Susan Hailpern; P Michael Ho; Virginia Howard; Brett Kissela; Steven Kittner; Daniel Lackland; Lynda Lisabeth; Ariane Marelli; Mary M McDermott; James Meigs; Dariush Mozaffarian; Michael Mussolino; Graham Nichol; Véronique L Roger; Wayne Rosamond; Ralph Sacco; Paul Sorlie; Véronique L Roger; Randall Stafford; Thomas Thom; Sylvia Wasserthiel-Smoller; Nathan D Wong; Judith Wylie-Rosett Journal: Circulation Date: 2009-12-17 Impact factor: 29.690
Authors: Hector M Dourron; Gary M Jacobson; James L Park; Jianhua Liu; Daniel J Reddy; Maria L Scheel; Patrick J Pagano Journal: Am J Physiol Heart Circ Physiol Date: 2004-09-23 Impact factor: 4.733
Authors: Craig B Harrison; Grant R Drummond; Christopher G Sobey; Stavros Selemidis Journal: Clin Exp Pharmacol Physiol Date: 2009-10-16 Impact factor: 2.557
Authors: H Rubbo; R Radi; M Trujillo; R Telleri; B Kalyanaraman; S Barnes; M Kirk; B A Freeman Journal: J Biol Chem Date: 1994-10-21 Impact factor: 5.157