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Kidney HIF‐1: Effects of altitude, exercise and cell‐free hemoglobin

Objective. To determine if hemoglobin‐based oxygen carriers (HBOC) improves kidney oxygenation during global hypoxia at rest and exercise. Methods. Relative tissue oxygenation was assessed by determining hypoxia‐inducible transcription factor 1 (HIF‐1) DNA‐binding (ELISA) and metabolic profiles (magnetic resonance spectroscopy) in Sprague Dawley rat kidneys. Animals were exposed to 1600 (NX) or 5500 (HX) m for 4 h, after treatment (3 ml) with either lactated Ringer's solution or hemoglobin‐based oxygen carrier (HBOC, 1300 mg/kg), during rest or after run to exhaustion. Results. At rest, HX‐induced HIF‐1 DNA‐binding was significantly reduced with HBOC treatment. In accordance, kidneys of animals at rest during HX showed evidence of oxidative stress, high hydroxybutyerate and low phosphotidyl choline. Oxidative stress was not apparent in the kidneys of HBOC‐treated animals during HX. HBOC had no effect on HIF‐1 DNA‐binding during NX. Exercise during NX increased HIF‐1 DNA binding, but lowered it during HX. HBOC‐treatment during exercise had no effect on kidney HIF activity. Conclusion. Data indicate that HBOC lowered HIF‐1 activity in the kidneys of rats exposed to 5500 m, as did exercise, and may provide a therapeutic measure by which to improve tissue oxygenation during global hypoxia. Funded by the USA Defense Advanced Research Project Agency (DARPA) #BAA 06‐19‐F64.