Acute stress augments obstructive apneas and related O2-desaturations in urethane-anesthetised rats via disruption of cholinergic modulation

Abstract

Obstructive sleep apnea (OSA) is a multifactorial respiratory disorder affecting nearly 1 billon of adults worldwide. Anomalies in respiratory control during sleep contribute to airway obstructions and recurrent desaturations; however, the origins of the problem are not well known. Stress disrupts brain function and increases the risk of OSA co-morbidities, including hypertension and obesity. Because, hypothalamic structures regulating the stress response also project to medullary areas regulating cardiorespiratory function and airway motor control, we hypothesised that exposure to a single stress session is suffcient to induce cardiorespiratory disturbances associated with OSA. Experiments were performed in urethane-anesthetised rats; this approach allows sleep-like brain state alternations with significant reductions in upper airway (genioglossus; GG), but not diaphragmatic (DIA), muscle tone during the transition from NREM-like to REM-like states. Adult male rats were either subjected to a 90 min session of immobilisation stress (n = 21) or handled briefly by the experimenter (n = 18). 24h later, rats were anesthetised (urethane, 1.6 g/kg; i.v.) and instrumented to monitor DIA and GG EMG. O2 saturation was measured by pulse oximetry (S pO2). Blood pressure was measured by an arterial catheter. Rats were placed in a supine position and respiratory airflow was measure by a temperature probe near the nares. Obstructive apneas were identified by the absence of airflow in the presence of DIA activity with a S pO2 drop greater than 3%. Stress did not affect distribution of sleep-like states or the state-related changes in phasic GG activity. However, stress augmented the incidence of obstructive apneas (0.5 vs 2.2 events/h; p = 0.05) and doubled the severity of desaturations associated with apneas (-6% vs -12% drop; p = 0.03). Pre-treatment with atropine (0.5 mg/kg) reduced obstructive apneas (drug effect: p = 0.04). Atropine blocked apnea-related O2 desaturations in stressed but not controls (apnea x stress x atropine: p = 0.04). Atropine treatment augmented GG activity; this effect was greater in NREM-like state, especially in stressed rats (atropine x state x stress: p = 0.05). We conclude that, in urethane anesthetised rats, stress disrupts cardiorespiratory control in ways that favor significant obstructive apneas. Disruption of cholinergic modulation of GG activity and cardiovascular function likely contributes to this process. These data point to an important factor in the onset of OSA. While the frequency of apneas was modest we propose that recurrent exposure to stressors or more significant events will worsen the condition over time. Supported by the Canadian Institutes of Health Research and the Foundation of the Québec Heart & Lung Institute. 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.