Background: Despite overwhelming evidence associating cigarette smoking with arterial stiffening, the precise mechanisms involved in this relationship are not fully understood. The aim of this study was to test the hypothesis that nicotine could increase aortic wave reflection and that this would be accompanied by an alteration in skin blood flow reactivity and a reduction in myocardial perfusion.

Materials and methods: We conducted a prospective study, divided into two experimental settings, in 21 healthy, non-smoker, male subjects. In the first setting (n=11), subjects received a placebo and a 2 mg nicotine tab, according to a randomized, double-blind, cross-over design. Each subject underwent measurements at baseline and for 1 hour post-nicotine or placebo, using the augmentation index (AIx) of the aortic pressure waveform to assess wave reflection. Endothelial function was evaluated twice, at baseline and 40 minutes after nicotine or placebo intake, using two hyperemic tests: skin heating (SkBF-H) and acetylcholine iontophoresis (SkBF-Ach). In the second experimental setting (n=10), subjects underwent an N-13 positron emission tomography (PET) study before and 60 minutes after 2 mg of nicotine, in order to quantify myocardial perfusion.

Results: Nicotine administration was associated with an increase in heart rate (HR) (P<0.001) and AIx corrected for HR (p=0.013) throughout the study. No microcirculatory effects of nicotine were observed on endothelial function as assessed by SkBF-h or SkBF-Ach. The subendocardial viability ratio was decreased (p=0.006), suggesting an impairment in myocardial perfusion induced by nicotine. This was confirmed by the N-13 PET studies, which revealed a reduction in resting myocardial perfusion (from 0.96 ± 0.07 to 0.84 ± 0.06 ml/min/g, p<0.05).

Conclusions: Nicotine does not impair endothelium-dependent microvascular vasomotricity. Nevertheless, exposure to small amounts of nicotine increase aortic wave reflection and reduces resting myocardial perfusion in non-smokers.