The experiments reported in this paper were designed to explain the phenomenon that plasma erythropoietin (Ep) levels reach peak titers after 8 hours of hypoxia and then fall to barely detectable levels after 72 hours. No single factor was found responsible for the decline of these levels with continued hypoxia, but both increase in the rate of erythropoiesis and increase in the hematocrit contribute to this phenomenon. No decrease in the rate of clearance of injected erythropoietin was observed in hypoxic rats, therefore, it is likely that the production of Ep decreased.

The fall in the plasma Ep level with continued hypoxia is not associated with decrease in the rate of erythropoiesis, suggesting that the initiation of increased erythropoiesis requires higher Ep levels than its maintenance during continued hypoxia. The reason for this difference remains speculative.

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