Airway hyperresponsiveness induced by intermittent hypoxia in rats

https://doi.org/10.1016/j.resp.2021.103787Get rights and content
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Highlights

  • AHR and lung inflammation occur after 14-day IH exposure in Brown Norway rats.

  • IH-induced AHR and lung inflammation are completely abolished by an antioxidant or a cyclooxygenase inhibitor.

  • Endogenous ROS and cyclooxygenase metabolites are responsible for these responses induced by IH.

Abstract

This study investigated whether intermittent hypoxia (IH) induces airway hyperresponsiveness (AHR) and associated with lung inflammation. Male Brown Norway rats were exposed to 14-day IH or room air (RA) for 6 h/day. One day after the last exposure, total lung resistance to various doses of methacholine was measured as an index of bronchoconstrictive responses. Compared with RA controls, methacholine significantly induced an augmented bronchoconstriction in IH-exposed rats. Moreover, IH exposure evoked lung inflammation which was reflected by increased inflammatory cell infiltration, concentrations of interleukin-6 and prostaglandin E2 in bronchoalveolar lavage fluid, and lung lipid peroxidation. IH-induced AHR and lung inflammation were completely abolished by daily intraperitoneal injection of N-acetylcysteine (an antioxidant) or ibuprofen (a cyclooxygenase inhibitor), but not by apocynin (an inhibitor of NADPH oxidase) or vehicle. In conclusion, AHR and lung inflammation occur after 14-day IH exposure, with endogenous reactive oxygen species and cyclooxygenase metabolites being responsible for these responses.

Keywords

Obstructive sleep apnea syndrome
Intermittent hypoxia
Airway hyperresponsiveness
Oxidative stress
Lung inflammation

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