Abstract
Adenosine plays a role in the energy supply of cells and provokes differential, hormone-like functions in circulating cells and various tissues. Its release is importantly regulated by oxygen tension. This renders adenosine and its kinetics interesting to investigate in humans subjected to low oxygen conditions. Especially for space exploration scenarios, hypoxic conditions – together with reduced gravity - represent two foreseen living conditions when planning manned long-duration space missions or planetary habitats. The PlanHab study investigated microgravity through inactivity in bed rest and normobaric hypoxia to examine their independent or combined effect on adenosine and its kinetics. Healthy male subjects (n = 14) completed three 21-day interventions: hypoxic bed rest (HBR); hypoxic ambulatory confinement (HAMB); normoxic bed rest (NBR). The interventions were separated by 4 months. Our hypothesis of a hypoxia-triggered increase in adenosine was confirmed in HAMB but unexpectedly also in NBR. However, the highest adenosine levels were noted following HBR. Furthermore, the percentage of hemolysis was elevated in HBR whereas endothelial integrity markers stayed low in all three interventions. In summary, these data suggest that neocytolysis accounts for these effects while we could reduce evidence for microcirculatory changes.
Highlights
The endogenous nucleosid adenosine exists ubiquitously in the intra- and extracellular space of the different organ tissues
The highest adenosine concentrations of over 200 nmol/l were observed in hypoxic bed rest (HBR) with a high statistical significance to baseline data was collected (BDC) at day 21 (p < 0.05 and p < 0.01)
After the end of the interventions adenosine concentrations remained elevated in all three groups with a statistical significance at R2 in normoxic bed rest (NBR) compared to BDC (p < 0.05)
Summary
The endogenous nucleosid adenosine exists ubiquitously in the intra- and extracellular space of the different organ tissues. Research on the effects of hypoxic environmental and living conditions in addition to reigning microgravity is of emerging interest for planning possible planetary habitats on the moon or Mars, or for long-duration space exploration class missions. In light of these scientific questions, the Planetary Habitat Simulation Study (PlanHab) was performed. We investigated the course of the adenosine release, its concentrations and that of its metabolite inosine and were further interested, if and to what degree the adaptation to these standardized living conditions are linked to adenosine profiles and different physiologic states. Our unexpected additional finding of hypoxia-independent adenosine increase has initiated further analysis to i) identify a potential role of hemolysis as a source of adenosine in our experimental interventions, ii) to evaluate the interaction of adenosine and endothelial barrier function, and iii) to investigate the impact of physical activity on adenosine concentrations
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