Mechanism of Erythropoietin Production by Cobaltous Chloride

Abstract

Abstract 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.