Erythropoietin production in normoxic and hypoxic rats with increased blood O₂ affinity

Effects of an acute increase in blood O₂ affinity on erythropoietin production were studied in normoxic and hypoxic male rats. Blood O₂ affinity was increased by exchange-transfusion with blood from sodium cyanate rats. P₅₀ was lowered to 27.6 torr (pH 7.4, P_CO2 = 40 Torr, 37°C) in the recipients compared to 41.8 torr in control rats exchange transfused with normal blood. Hypoxia was induced by exposure to simulated high altitude (4750 or 7000 m) for 16 h. Erythropoietin was determined by in vivo bioassay. In rats with normal blood O₂ affinity, plasma erythropoietin was undetectable at 300 m, 0.26 ± 0.10 U/ml at 4750 m (mean ± SEM; n = 7)_, and 3.52 ± 0.58 U/ml at 7000 m (n = 10)). Plasma erythropoietin titers were significantly ehanced in rats with high blood O₂ affinity at 300 m 0.05 ± 0.01 U/ml; n = 4) and moderately increased at 4750 m (0.57 ± 0.12 U/ml; n = 7), but unchanged at 7000 m (3.88 ± 0.74 U/ml; n = 10). These results indicate that a high blood O₂ affinity reduces the O₂ delivery to the cells controlling eryhtropoietin production in normaxia and moderate hypoxia. However, this is offset at serve hypoxia most likely by an improved O₂ loading to the blood.