NADPH oxidase 2 is necessary for chronic intermittent hypoxia‐induced sternohyoid muscle weakness in adult male mice

Abstract

Exposure to chronic intermittent hypoxia (CIH) evokes redox changes, culminating in impaired upper airway muscle function. We sought to determine if NADPH oxidase 2 (NOX2)-derived reactive oxygen species underpin CIH-induced maladaptive changes in upper airway (sternohyoid) muscle performance. Adult male mice (C57BL/6J) were assigned to one of three groups: normoxic controls (sham); CIH-exposed (CIH, 12 cycles/hour, 8 h/day for 14 days); and CIH + apocynin (NOX2 inhibitor, 2 mM) given in the drinking water throughout exposure to CIH. In addition, we studied sham and CIH-exposed NOX2-null mice (B6.129S-CybbTM 1Din/J ). Profound sternohyoid muscle dysfunction following exposure to CIH was entirely prevented by apocynin cotreatment or NOX2 deletion. Exposure to CIH increased sternohyoid muscle NOX enzyme activity, with no alteration to the gene or protein expression of NOX subunits.There was no evidence of overt oxidative stress, muscle regeneration, inflammation or atrophy following exposure to CIH. We suggest that NOX-dependent CIH-induced upper airway muscle weakness increases vulnerability to upper airway obstruction.Our results have implications for human obstructive sleep apnoea syndrome and point to antioxidant intervention, potentially targeting NOX2 blockade, as a therapeutic strategy.