Background: The peripheral chemoreflex contributes to cardiovascular regulation and represents the first line of defense against hypoxia. The effects of nicotine on chemoreflex regulation in non-smoking humans are unknown. Method: We conducted a prospective, randomized, crossover, and placebo controlled study in 20 male non-smokers to test the hypothesis that nicotine increases chemoreflex sensitivity. The effects of two intakes of 2 mg nicotine tabs and placebo on sympathetic nerve activity to muscle circulation (MSNA), minute ventilation (Ve), blood pressure (BP) and heart rate (HR) were assessed during normoxia, moderate isocapnic hypoxia, hyperoxic hypercapnia and an isometric handgrip in 10 subjects. Maximal end expiratory apneas were performed at baseline and at the end of the fifth minute of hypoxia. In a second experimental setting, we studied the ventilatory response to a more marked isocapnic hypoxia in 10 other volunteers.

Results: Mean MSNA and Ve were not modified by nicotine during the 5 minutes of normoxia or moderate hypoxia. However, in the presence of nicotine MSNA was related to oxygendesaturation (p < 0.01). The sympathoexcitatory effects of nicotine became especially evident when apneas achieved oxygen saturations less than 85% (511  44% increase in MSNA after the first intake, and 436  43% increase after the second intake, vs. 387  56% and 338  31% with placebo, respectively, p < 0.05). Nicotine also increased the ventilatory response compared to placebo when oxygen saturation decreased to less than 85% (p < 0.05). Conclusion: This is the first study to demonstrate that nicotine increases peripheral chemoreflex sensitivity to large reductions in arterial oxygen content in healthy non-smokers.