Effect of hypoxia exposure on the phenotypic adaptation in remodelling skeletal muscle submitted to functional overload

AimTo determine whether hypoxia influences the phenotypic adaptation of skeletal muscle induced by mechanical overload. MethodsPlantaris muscles of female rats were submitted to mechanical overload following synergist ablation. After 3days of overload, rats were exposed to either hypobaric hypoxia (equivalent to 5500m) or normoxia. Muscles were collected after 5, 12 and 56days of overload (i.e. after 3, 9 and 53days of hypoxia). We determined the myosin heavy chain (MHC) distribution, mRNA levels of myocyte-enriched calcineurin-integrating protein 1 (MCIP1) to indirectly assess calcineurin activity, the changes in oxidative capacity from the activities of citrate synthase (CS) and cytochrome c oxidase (COX), and the expression of regulators involved in mitochondrial biogenesis (Pgc-1, NRF1 and Tfam) and degradation (BNIP-3). ResultsHypoxia did not alter the fast-to-slow MHC shift and the increase in calcineurin activity induced by overload; it only transiently slowed down the overload-induced transition in MHC isoforms. Hypoxia similarly decreased CS and COX activities in overloaded and control muscles. Nuclear respiratory factor 1 (NRF1) and transcription factor A (Tfam) mRNA and BNIP-3 protein were not influenced by hypoxia in overloaded muscles, whereas Pgc-1 mRNA and protein contents did not correlate with changes in oxidative capacity. ConclusionHypoxia is not a critical stimulus to modulate the fast-to-slow MHC transition associated with overload. Thus, the impairment of the fast-to-slow fibre shift often observed during post-natal development in hypoxia could be explained by the lower voluntary locomotor activity associated with hypoxia. Hypoxia alters mitochondrial oxidative capacity, but this adaptive response is similar in overloaded and control muscles.