Striated cardiac and skeletal muscle have distinct responses to acute and chronic hypoxia

Introduction: Striated muscle (skeletal- SkM and cardiac right and left ventricles- RV, LV) composes over 40 percent of mammalian organisms and are responsible for coordinated delivery of blood and locomotion. Although the underlying structure and primary contractile functions are similar between these muscle types, in many other ways they are fundamentally distinct including in their response to stress. Purpose: To identify the differences in the striated muscle (RV, LV, and SkM) response to hypoxia. We set out to quantify changes in striated muscle mass and in the cellular response to hypoxia including activation of the hypoxia-inducible factor-1 α (HIF-1α) signaling cascade. Methods: Male and female C57BL6 mice were placed in a hypobaric hypoxia chamber (HH; 17,000’) for four weeks (chronic hypoxia), three days (acute hypoxia), or remained at ambient air. Histology and morphometric analyses were used to quantify changes in muscle mass. Changes in local oxygen were quantified by hypoxyprobe. Expression of HIF-1α signaling was quantified by western blotting and qRT-PCR. Results: In response to chronic hypoxia, the RV underwent significant hypertrophy, the SkM underwent significant atrophy, and the LV remained mass stable. In response to acute hypoxia, the RV underwent hypertrophy, LV mass remained stable while the SkM underwent slight atrophy. The chronic hypoxia RV demonstrated the most robust changes in local oxygen by hypoxyprobe. Molecular adaptations to hypoxia (HIF-1α and its gene targets) also differed by striated muscle type. Conclusion: Striated muscle has a tissue-specific response to hypoxia. Understanding these specific mechanisms is important to help combat the multitude of hypoxic human diseases and for translation to individuals that live at or journey to high altitudes. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.