Chronic Intermittent Hypoxia-Induced Diaphragm Muscle Weakness Is NADPH Oxidase-2 Dependent

Chronic intermittent hypoxia (CIH)-induced redox alterations underlie diaphragm muscle dysfunction. We sought to establish if NADPH oxidase 2 (NOX2)-derived reactive oxygen species (ROS) underpin CIH-induced changes in muscle, which manifest as impaired performance. Adult male mice (C57BL/6J) were assigned one of three groups: normoxic controls (sham); chronic hypoxia-exposed (CIH, 12 cycles/hour, 8 h/day for 14 days); and CIH + apocynin (NOX2 inhibitor, mM) administered the drinking water throughout exposure CIH. In separate studies, we examined sham CIH-exposed NOX2-null (B6.129S-CybbTM1Din/J). Apocynin co-treatment or NOX2 deletion proved efficacious entirely preventing dysfunction following Exposure had no effect on expression. However, NOX4 mRNA expression was increased wild-type null mice. There evidence overt oxidative stress. A NOX2-dependent increase genes related regeneration, antioxidant capacity, autophagy atrophy evident suggest that NOX-dependent weakness has potential affect ventilatory non-ventilatory performance respiratory system. Therapeutic strategies employing blockade may function an adjunct therapy improve reduce disease burden diseases characterised by CIH, such obstructive sleep apnoea.