Contribution of nicotine to acute endothelial dysfunction in long-term smokers

AbstractObjectivesThe aim of this study was to determine whether nicotine, a constituent of cigarette smoke, contributes to acute endothelial dysfunction after smoking one cigarette.BackgroundAnimal studies suggest that nicotine might cause an impairment of endothelium-dependent vasodilation via an increase in oxidative stress.MethodsSixteen healthy smokers were entered into a randomized, observer-blinded crossover study comparing the effects of nicotine nasal spray (1-mg nicotine) and cigarette smoke (1-mg nicotine, 12 mg tar) on vascular reactivity in the brachial artery. Using high-resolution ultrasound, flow-mediated dilation (FMD) and endothelium-independent, nitroglycerin-induced dilation were assessed at baseline and 20 min after the administration of nicotine (spray or cigarette).ResultsIn response to similar increases in nicotine serum levels, FMD values declined from 10.2 ± 4.4% to 6.7 ± 4.0% after the spray (mean difference: −3.6 ± 2.0%, 95% confidence interval: −4.6; −2.5, p < 0.0001) and from 9.4 ± 3.8% to 4.3 ± 2.8% after the cigarette (−5.1 ± 2.6%, −6.5; −3.7, p < 0.0001). Nitroglycerin-induced dilation remained similar within both periods. Performing a period effect analysis of variance, a significant influence on FMD was found for the mode of administration (p = 0.017) and the baseline value (p = 0.021). The effect on FMD was more pronounced after the cigarette than after the spray (estimated average effect difference: 1.9% FMD). Oxidation parameters did not increase significantly after nicotine spray or tobacco exposure.ConclusionsThese results demonstrate that nicotine alone causes acute endothelial dysfunction, although to a lesser extent than smoking a cigarette of the same nicotine yield. However, the precise mechanisms by which nicotine leads to this altered vascular reactivity remain unclear