Chronic, episodic nicotine exposure enhances the hypoxic ventilatory response in adult female rats

It is well known that cigarette smoking causes lung disease and damages the airways. However, we know little about the direct role of nicotine, the primary addictive component of tobacco, in the development of smoking- related diseases. Along with promoting cancer cell proliferation and airway inflammation, nicotine can modulate central respiratory control, increasing the rate and depth of breathing through mechanisms that are not well understood. In addition, cigarette smoking is associated with obstructive sleep apnea, a sleep-related breathing disorder that is marked by reduced brainstem respiratory motor output. Despite these examples indicating that chronic nicotine exposure in adulthood may alter central respiratory control, there is no published research that directly tests this hypothesis. We exposed male and female adult rats to nicotine for four weeks through their drinking water and then used whole body plethysmography to test the hypothesis that chronic, episodic nicotine exposure alters restful breathing and the hypoxic ventilatory response (HVR), a critical respiratory chemoreflex. We measured tidal volume (TV) and frequency of breathing at rest, and during a 5- minute episode of hypoxia (10% oxygen/balance nitrogen). Total ventilation (VE/VCO 2 ) was calculated as TV X Frequency and normalized to carbon dioxide production, to account for changes in metabolism, and body weight. For both males and females, comparisons were made between groups and across trials using a 2-way ANOVA and Tukey’s post-hoc test. In male rats, nicotine exposure significantly decreased overall ventilation at rest in one of three trials (Trial 1 VE/VCO 2 : Nicotine exposed, 30.7±7.5 mL/min/100g, Control, 44.3±6.4 mL/min/100g, p=0.0183), but had no effect on breathing during hypoxia. In female rats, nicotine exposure had no effect on breathing at rest, however, overall ventilation during hypoxia was enhanced in nicotine exposed rats compared to controls in two of three trials (Trial 1 VE/VCO 2 : Nicotine exposed, 106.8±20.6 mL/min/100g, Control, 79.8±5.1 mL/min/100g, p=0.049; Trial 3 VE/VCO 2 : Nicotine exposed, 101.6±9.9 mL/min/100g, Control, 68.1±10.9 mL/min/100g, p=0.007). Overall, these results suggest that chronic nicotine exposure triggers plasticity in the chemoreflex pathway mediating the HVR in a sex specific manner and further studies are warranted to understand the implications of this finding. 1K99HL164973-02. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.