Aim: Experiments have indicated that skin perfusion in mice is sensitive to reductions in environmental O-2 availability. Specifically, a reduction in skin-surface PO2 attenuates transcutaneous O-2 diffusion, and hence epidermal O-2 supply. In response, epidermal HIF-1 alpha expression increases and facilitates initial cutaneous vasoconstriction and subsequent nitric oxide-dependent vasodilation. Here, we investigated whether the same mechanism exists in humans. Methods: 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 O-2-enriched (42%) breathing gas (Hypoxia(Skin)), and once barometric pressure and inspired O-2 fraction were normal (Control(1)). In a second experiment, nine males rested for 8 h with both forearms wrapped in plastic bags. O-2 was expelled from one bag by nitrogen flushing (Anoxia(Skin)), whereas the other bag was flushed with air (Control(2)). In both experiments, skin blood flux was assessed by laser Doppler on the dorsal forearm, and HIF-1 alpha expression was determined by immunohistochemical staining in forearm skin biopsies. Results: Skin blood flux during Hypoxia(Skin) and Anoxia(Skin) remained similar to the corresponding Control trial (P = 0.67 and P = 0.81). Immunohistochemically stained epidermal HIF-1 alpha was detected on 8.2 +/- 6.1 and 5.3 +/- 5.7% of the analysed area during Hypoxia(Skin) and Control(1) (P = 0.30) and on 2.3 +/- 1.8 and 2.4 +/- 1.8% during Anoxia(Skin) and Control(2) (P = 0.90) respectively. Conclusion: Reductions in skin-surface PO2 do not affect skin perfusion in humans. The unchanged epidermal HIF-1 alpha expression suggests that epidermal O-2 homoeostasis was not disturbed by Hypoxia(Skin)/Anoxia(Skin), potentially due to compensatory increases in arterial O-2 extraction.
