Contractile Activity Is Necessary to Trigger Intermittent Hypobaric Hypoxia-Induced Fiber Size and Vascular Adaptations in Skeletal Muscle

Abstract

Altitude training has become increasingly popular in recent decades. Its central and peripheral effects are well-described; however, few studies have analyzed the effects of intermittent hypobaric hypoxia (IHH) alone on skeletal muscle morphofunctionality. Here, we studied the effects of IHH on different myofiber morphofunctional parameters, investigating whether contractile activity is required to elicit hypoxia-induced adaptations in trained rats. Eighteen male Sprague-Dawley rats were trained 1 month and then divided into three groups: (1) rats in normobaria (trained normobaric inactive, TNI); (2) rats subjected daily to a 4-h exposure to hypobaric hypoxia equivalent to 4,000 m (trained hypobaric inactive, THI); and (3) rats subjected daily to a 4-h exposure to hypobaric hypoxia just before performing light exercise (trained hypobaric active, THA). After 2 weeks, the tibialis anterior muscle (TA) was excised. Muscle cross-sections were stained for: (1) succinate dehydrogenase to identify oxidative metabolism; (2) myosin-ATPase to identify slow- and fast-twitch fibers; and (3) endothelial-ATPase to stain capillaries. Fibers were classified as slow oxidative (SO), fast oxidative glycolytic (FOG), fast intermediate glycolytic (FIG) or fast glycolytic (FG) and the following parameters were measured: fiber cross-sectional area (FCSA), number of capillaries per fiber (NCF), NCF per 1,000 μm2 of FCSA (CCA), fiber and capillary density (FD and CD), and the ratio between CD and FD (C/F). THI rats did not exhibit significant changes in most of the parameters, while THA animals showed reduced fiber size. Compared to TNI rats, FOG fibers from the lateral/medial fields, as well as FIG and FG fibers from the lateral region, had smaller FCSA in THA rats. Moreover, THA rats had increased NCF in FG fibers from all fields, in medial and posterior FIG fibers and in posterior FOG fibers. All fiber types from the three analyzed regions (except the posterior FG fibers) displayed a significantly increased CCA ratio compared to TNI rats. Global capillarisation was also increased in lateral and medial fields. Our results show that IHH alone does not induce alterations in the TA muscle. The inclusion of exercise immediately after the tested hypoxic conditions is enough to trigger a morphofunctional response that improves muscle capillarisation.

Physiological Effects of Intermittent Passive Exposure to Hypobaric Hypoxia and Cold in Rats

“…Nevertheless, after a longer period of hypoxia (6 weeks), fiber capillarity increased in all studied muscles (DIA, SOL, EDL, and TA), and no changes or increases in FCSA were reported , confirming the importance of hypoxic dose (exposure time) and the activity in the muscle responses. Thus, our results confirm that IHH at rest did not produce angiogenesis, which may be due to the lack of adequate metabolic or mechanical stimuli necessary to show capillary growth (Deveci et al, 2001aRizo-Roca et al, 2018). Analyzing HIF-1α signaling pathway modulation in HYPO, VEGF protein presented a tendency toward higher expression than CTRL.…”

“…These changes in SO and FOG fiber morphometry indicate that the hypoxic stimulus reduced capillary domain area and diffusion distance in fibers with a predominant oxidative metabolism. It has been shown that hypoxia per se is not able to produce angiogenesis in the skeletal muscle, exercise or activity being necessary to activate the angiogenic process (Jackson et al, 1987;Deveci et al, 2001a;Rizo-Roca et al, 2018). Deveci et al (2001a) conducted some experiments in which chronic normobaric hypoxia was applied during different time periods.…”

Physiological and Biological Responses to Short-Term Intermittent Hypobaric Hypoxia Exposure: From Sports and Mountain Medicine to New Biomedical Applications

“…Finally, a recently published meta-analysis on the effect of natural or simulated altitude training in team-sport athletes conclude that hypoxic intervention appears to be a worthwhile training strategy for improvement in team-sport athletes, with enhanced performance over control groups persisting for at least 4 weeks post-intervention (Hamlin et al, 2018 ). Also, our recent data indicate that contractile activity seems to be necessary to trigger in skeletal muscle the adaptive responses induced by intermittent exposure to hypoxia (Rizo-Roca et al, 2018 ).…”

BREATHE DMD: boosting respiratory efficacy after therapeutic hypoxic episodes in Duchenne muscular dystrophy

“…Paradigms of chronic intermittent hypoxia (mirroring sleep apnoea and respiratory diseases) must clearly be avoided given their deleterious effects on skeletal muscle function (Attaway et al., 2023; Drummond et al., 2022; 2023; O'Halloran, 2016; O'Halloran & Lewis, 2017). However, hypoxia‐dependent muscle metabolic reprogramming and angiogenesis (Clanton & Klawitter, 2001; Drozdovska et al., 2023; Li et al., 2020; Rizo‐Roca et al., 2018; Suzuki, 2016) could plausibly confer benefit to dystrophic respiratory muscles, with consequences for system performance. A body of work is required to establish the effects of AIH paradigms on respiratory muscle.…”