Mechanism of Erythropoietin Production by Cobaltous Chloride

Normal and nephrectomized Sprague-Dawley rats were treated with CoCl₂ at three dose levels, 10, 20, and 25 µm/ 100 g body weight. The effects of this drug on acid-base balance were related to the production of erythropoietin. Within 6 hr after the administration of CoCl₂ to normal rats, a dose-related respiratory alkalosis occurred associated with an increase in the affinity of hemoglobin for oxygen. This was followed by an increase in the production of erythropoietin. Nephrectomy altered the acid-base balance of the animal such that a profound acidosis occurred after the administration of CoCl₂ with an associated decrease in the affinity of hemoglobin for oxygen. Erythropoietin could not be detected in these nephrectomized rats given CoCl₂. These findings demonstrate that the production of erythropoietin after the administration of CoCl₂ is related in significant measure to changes in acid-base balance with its subsequent effect on the affinity of hemoglobin for oxygen.