Mechanism of erythropoietin production by cobaltous chloride.

Normal and nephrectomized SpragueDawley rats were treated with CoCI2 at three dose levels, 10, 20, and 25 tm/ 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 CoCI2 to normal rats, a dose-related respiratory alkalosis occurred associated with an increase in the affinity of hemoglobin for oxygen. This was followed by ag, 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 CoCI2 with an associated decrease in the affinity of hemoglobin for oxygen. Erythropoietin could not be detected in these nephrectomized rats given Cod2. These findings demonstrate that the production of erythropoietin after the administration of CoCI2 is related in significant measure to changes in acid-base balance with its subsequent effect on the affinity of hemoglobin for oxygen.