Molecular aspects of improving physical performance in conditions of short-term hypobaric hypoxia and pharmacological pseudohypoxia

Background. Hypoxic training are actively used in both professional and amateur sports. Hypoxia triggers a number of adaptive mechanisms aimed at improving stamina. However, these compensatory and adaptive pathways can be activated through rational pharmacological exposure, inducing pseudohypoxia.

The aim of the study was to compare the molecular mechanisms of performance enhancement in short-term hypobaric hypoxia and pharmacological pseudohypoxia.

Material and methods. Hypobaric hypoxia was simulated in male C57BL/6 mice by placing the animals in a pressure chamber with 14% oxygen content and reduced atmospheric pressure (equivalent to 4000 m above sea level). Pseudohypoxia was reproduced by a course of administration of a succinate dehydrogenase inhibitor – sodium polydihydroxyphenylene thiosulfonate, orally at a dose of 2.1 mg/kg. A combined exposure option was also simulated in animals: hypoxia + pseudohypoxia. After 21 days, the level of physical activity of the animals was recorded in the forced swimming test. Next, the concentrations of Hif-1α, AMP-activated protein kinase, and insulin receptors in muscle tissue, as well as erythropoietin, insulin-like growth factor-1, and cortisol in blood serum were evaluated.

Results. It has been shown that both in conditions of hypobaric hypoxia and pharmacological pseudohypoxia, as well as their combined variants, there is an increase in the concentration of Hif-1α, AMP-activated protein kinase and insulin receptors in muscle tissue. An increase in serum erythropoietin concentration of 51.8% (p < 0.05) was noted in hypobaric hypoxia, which was not observed in the case of pseudohypoxia and combined exposure. It is also worth noting that the physical performance of the animals to which the combined treatment option was applied was significantly higher than in mice that were simulated hypoxia (by 41.8%; p < 0.05) and pseudohypoxia (by 64.1%; p < 0.05). Cortisol concentration are not change in all groups.

Conclusion. In order to increase the level of physical activity through the activation of Hif-1α and insulin-dependent cellular signaling mechanisms, it is advisable to combine hypobaric hypoxic effects and pharmacological pseudohypoxia.