Cutaneous exposure to hypoxia does not affect skin perfusion in humans.
Experiments have indicated that skin perfusion in mice is sensitive to reductions in environmental O2availability. Specifically, a reduction in skin-surface PO2attenuates transcutaneous O2diffusion, and hence epidermal O2supply. In response, epidermal HIF-1α expression increases and facilitates initial cutaneous vasoconstriction and subsequent nitric oxide-dependent vasodilation. Here, we investigated whether the same mechanism exists in humans.



In a first experiment, eight males rested twice for 8 h in a hypobaric chamber. Once, barometric pressure was reduced by 50%, while systemic oxygenation was preserved by O2-enriched (42%) breathing gas (HypoxiaSkin), and once barometric pressure and inspired O2fraction were normal (Control1). In a second experiment, nine males rested for 8 h with both forearms wrapped in plastic bags. O2was expelled from one bag by nitrogen flushing (AnoxiaSkin), whereas the other bag was flushed with air (Control2). In both experiments, skin blood flux was assessed by laser Doppler on the dorsal forearm, and HIF-1α expression was determined by immunohistochemical staining in forearm skin biopsies.



Skin blood flux during HypoxiaSkinand AnoxiaSkinremained similar to the corresponding Control trial (P = 0.67 and P = 0.81). Immunohistochemically stained epidermal HIF-1α was detected on 8.2 ± 6.1 and 5.3 ± 5.7% of the analysed area during HypoxiaSkinand Control1(P = 0.30) and on 2.3 ± 1.8 and 2.4 ± 1.8% during AnoxiaSkinand Control2(P = 0.90) respectively.



Reductions in skin-surface PO2do not affect skin perfusion in humans. The unchanged epidermal HIF-1α expression suggests that epidermal O2homoeostasis was not disturbed by HypoxiaSkin/AnoxiaSkin, potentially due to compensatory increases in arterial O2extraction.
Department of Environmental Physiology, School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden.
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Siebenmann
Department of Environmental Physiology, School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden.
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Keramidas
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
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Rundqvist
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
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Mijwel
Departments of Physiology, Development and Neuroscience and Medicine, University of Cambridge, Cambridge, UK.
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Cowburn
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.|Departments of Physiology, Development and Neuroscience and Medicine, University of Cambridge, Cambridge, UK.
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Johnson
Department of Environmental Physiology, School of Technology and Health, Royal Institute of Technology, Stockholm, Sweden.
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O
Eiken
D000328:Adult; D001274:Atmospheric Pressure; D004921:Erythropoietin / Q000097:blood; D064368:Healthy Volunteers; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D009573:Nitrites / Q000097:blood; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D055815:Young Adult
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009573:Nitrites; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin
altitude; hypoxia-inducible factor-1α; nitric oxide; skin blood flow; vasoconstriction; vasodilation