Dependence of erythropoietin production on blood oxygen affinity and hemoglobin concentration in rats

Plasma erythropoietin titers (Ep) were compared in rats subjected to different kinds of systemic hypoxia. Ep increased exponentially, when hypoxia was induced by exposure to simulated altitude (from <0.025 IU Ep/ml plasma at sea-level up to 3.65 IU EP/ml at 7000 m). An acute increase in the O₂ affinity of blood augmented Ep production in normal rats but not in rats exposed to hypobaria. Ep also rose exponentially when isovolemic anemia was induced (e.g., 0.5 IU Ep/ml plasma were found at 7 g Hb/dl blood). When the same reduction in blood O₂ carrying capacity was produced by CO-inhalation (0.1% CO in air), Ep increased to 5.57 IU/ml plasma. This very high value was considered to be partly due to the very high O₂ affinity of carboxyhemoglobin. These results indicate that a left shift in the hemoglobin-O₂ dissociation curve produces a stimulation of Ep production, particularly, when the O₂-carrying capacity of blood is lowered.