Greater γ-tocopherol status during acute smoking abstinence with nicotine replacement therapy improved vascular endothelial function by decreasing 8-iso-15(S)-prostaglandin F2α

Abstract

Nicotine replacement therapy (NRT) improves the long-term success rate of smoking cessation, but induces oxidative stress and inflammatory responses that may delay the restoration of vascular endothelial function (VEF). No studies have examined co-therapy of NRT-assisted smoking abstinence with γ-tocopherol (γ-T), a vitamin E form with antioxidant and anti-inflammatory activities, on improvements in VEF. In a randomized, double-blind, placebo-controlled study, healthy smokers (25 ± 1 y old; mean ± SEM) received NRT and abstained from smoking for 24 h with placebo (n = 12) or oral administration of γ-T-rich mixture of tocopherols (γ-TmT; n = 11) that provided 500 mg γ-T. Brachial artery flow-mediated dilation (FMD), and biomarkers of nitric oxide metabolism, antioxidant status, inflammation, and lipid peroxidation [8-iso-prostaglandin F2α stereoisomers (8-iso-15(R)-PGF2α and 8-iso-15(S)-PGF2α)] were measured prior to and after 24 h of smoking abstinence. Smoking abstinence with NRT regardless of γ-TmT similarly decreased urinary naphthol (P < 0.05) without affecting plasma cotinine. γ-TmT increased plasma γ-T by 4-times and the urinary metabolite of γ-T, γ-carboxyethyl-chromanol, by three times. Smoking abstinence with γ-TmT, but not smoking abstinence alone, increased FMD without affecting plasma nitrate/nitrite or the ratio of asymmetric dimethylarginine/arginine. Urinary 8-iso-15(S)-PGF2α decreased only in those receiving γ-TmT and was inversely correlated to FMD (R = -0.43, P < 0.05). Circulating markers of inflammation were unaffected by smoking abstinence or γ-TmT. Short-term NRT-assisted smoking abstinence with γ-TmT, but not NRT-assisted smoking abstinence alone, improved VEF by decreasing 8-iso-15(S)-PGF2α, a vasoconstrictor that was otherwise unaffected by NRT-assisted smoking abstinence.

Trial registration: ClinicalTrials.gov NCT01314443.

Keywords: Vascular endothelial function; flow-mediated dilation; nicotine replacement therapy; smoking cessation; vitamin E.

© 2014 by the Society for Experimental Biology and Medicine.

Figures

Figure 1

Plasma cotinine and urinary naphthol, plasma tocopherols, and flow-mediated dilation (FMD) responses in healthy smokers following 24 h smoking abstinence with (n = 11) or without (n = 12) γ-tocopherol-rich mixture of tocopherols (γ-TmT). (a) Plasma α- and γ-tocopherol concentrations, (b) plasma cotinine and urinary naphthol concentrations, and (c) FMD responses expressed as absolute change and percent change from baseline diameter in smokers following smoking abstinence with or without oral administration of γ-TmT. T: time; γ-TmT × T: γ-TmT × time interaction. Bars are means ± SEM. Means not sharing a common superscript are significantly different (P < 0.05)