Nicotine increases chemoreflex sensitivity to hypoxia in non-smokers

Background The peripheral chemoreflex contributes to cardiovascular regulation and represents the first line of defence 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 (muscle sympathetic nerve activity; MSNA), minute ventilation (Ve), blood pressure and heart rate were assessed during normoxia, moderate isocapnic hypoxia, hyperoxic hypercapnia and an isometric handgrip in 10 subjects. Maximal end-expiratory apnoeas 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 min of normoxia or moderate hypoxia. In the presence of nicotine MSNA was related to oxygen desaturation (P < 0.01). The sympathoexcitatory effects of nicotine became especially evident when apnoeas achieved oxygen saturations less than 85% (511 +/- 44% increase in MSNA after the first intake, and 436 +/- 43% increase after the second intake versus 387 +/- 56% and 338 +/- 31% with placebo, respectively, P < 0.05). Nicotine also increased the ventilatory response compared with 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.