Abstract

The administration of cobalt (250 µmol/kg s.c.) or exposure to hypoxia (0.42 atm) produced an elevation in blood lactic acid (lactate) levels in rats. Cobalt treatment produced a rise in blood lactate levels which peaked at a single time interval reaching a maximum witihin an hour after injection (230% of control) and which returned to control levels within 3 hours. However, hypoxia produced two peaks in blood lactate levels (180% of control), one occurring during the first 30 minutes and the second occurring after 8 to 9 hours exposure. Each peak of blood lactate produced by cobalt or hypoxia preceded increases in renal cortical adenosine 3', 5'-monophosphate (cyclic AMP) levels. No change in cyclic nucleotide content was observed in the renal medulla. Subsequent to each rise in blood lactate and renal cyclic AMP concentrations, an increase in plasma erythopoietin titers was also observed. In vitro enzymatic experiments demonstrated that lactate produced a 2-fold increase in renal cortical adenylate cyclase activity although the activity of the medullary enzyme was unaltered. This profile of enzymatic activity correlates with the effects seen on cyclic AMP levels in vivo following either cobalt treatment or exposure to hypoxia. Additionally, lactate produced an increase in ⁵⁹Fe incorporation into red blood cells of polycythemic mice, whereas pyruvate was without any effect in this system. These data indicate that lactate stimulates erythropoiesis and further suggest that the effects of cobalt or hypoxia on kidney erythropoietin production may be modulated by a lactate-induced alteration in renal cortical adenylate cyclase activity.