Ethanol abolishes ventilatory long-term facilitation and blunts the ventilatory response to hypoxia in female rats.

Obstructive sleep apnea (OSA) is a breathing disorder in which airway obstruction during sleep leads to periodic bouts of inadequate (hypopneic) or absent (apneic) ventilation despite neurorespiratory effort. Repetitive apneic and hypopneic exposures can induce intermittent hypoxemia and lead to a host of maladaptive behavioral and physiological outcomes. Intermittent hypoxia treatment (IH), which consists of alternating exposure to hypoxic and normal air, can induce a long-lasting increase in breathing motor outputs called long term facilitation (LTF). IH models key aspects of the hypoxemia experienced during OSA and LTF might serve to prevent OSA or ameliorate its severity by stimulating ventilatory output during or after apnea/hypopnea. Ethanol consumption prior to sleep exacerbates existing OSA, but it is unknown how ethanol affects LTF expression. Thus, we hypothesized that ethanol treatment would attenuate LTF expression and the magnitude of the ventilatory response during acute hypoxic exposure. We administered either low-dose (0.8 g/kg) or high-dose (3 g/kg) ethanol or saline to adult female Sprague-Dawley rats through intraperitoneal injection and then measured subjects' ventilatory output by whole-body plethysmography during baseline, a 5 by 3-minute moderate IH protocol (hypoxia: F_iO₂ = 0.11, Normoxia: room air), and for one hour following the end of IH. Results indicate that low-dose ethanol abolishes LTF of respiratory rate and minute ventilation and trends suggest that low-dose ethanol might attenuate respiratory rate and minute ventilation during acute hypoxic exposure. While high-dose ethanol significantly diminished subjects' respiratory rate and minute ventilation during hypoxia, LTF expression was not significantly different between high-dose ethanol and saline-treated subjects. Overall, data indicate that ethanol exposure dramatically attenuates LTF expression following IH treatment and impairs ventilatory responses to hypoxia in a dose-dependent manner. Such findings inspire further consideration of ethanol's negative effects upon endogenous compensatory mechanisms for repeated hypoxic exposure, both in the context of OSA and beyond.