Heat Acclimation Protects Skeletal Muscle from Hypobaric Hypoxia via Modulation of Redox, Proteolytic and Myogenic...

Hypobaric hypoxia induces skeletal muscle atrophy through oxidative stress, inflammation, and activation of proteolytic pathways, contributing to reduced physical performance at high altitude. Heat acclimation has been proposed to induce cross-tolerance against diverse stressors through shared cellular adaptive mechanisms. The present study investigated whether prior heat acclimation induces protective effect against hypoxia-induced skeletal muscle degeneration. Male Sprague Dawley rats underwent short term (5 days) and long term (30 days) passive heat acclimation (34 ± 1°C) followed by 7 days of hypobaric hypoxia exposure (25,000 ft). The gastrocnemius muscles were analysed for oxidative stress, antioxidant defense, molecular chaperones, proteolytic markers, muscle damage markers, myogenic proteins, and apoptotic markers and histological alterations. Hypoxia exposure induced significant skeletal muscle atrophy characterised by increased oxidative stress, intracellular calcium accumulation, NF-ĸB activation, and upregulation of muscle-specific E3 ligases, Murf-1 and Mafbx, accompanied by enhanced apoptotic signalling and suppression of myogenic markers. Prior heat acclimation markedly attenuated these alterations, with long term heat acclimation showing greater efficacy. Heat acclimation enhanced HSP70 and HSP90 expression along with antioxidant capacity, reduced oxidative damage, suppressed proteolytic damage, and preserved myogenic protein expression and overall morphology of muscle fibres. These findings demonstrate that heat acclimation induces a cytoprotective phenotype that confers cross-tolerance to hypobaric hypoxia by modulating redox balance, proteolysis and apoptotic pathways thereby preserving skeletal muscle integrity. These cytoprotective adaptations were more pronounced following long-term heat acclimation compared with short- term heat acclimation. Long-term heat acclimation may represent a practical non-pharmacological strategy to mitigate hypoxia-induced muscle atrophy.