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 treated rats. P50 was lowered to 27.6 torr (pH 7.4, PCO2 = 40 torr, 37 degrees 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 enhanced 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 erythropoietin production in normoxia and moderate hypoxia. However, this is offset at severe hypoxia most likely by an improved O2 loading to the blood.