Biochemical Basis of Heart Function. X. Reduction in the Na+–K+-Stimulated ATPase Activity in Failing Rat Heart Due to Hypoxia

Abstract

The activities of the membrane bound enzyme Na+–K+-stimulated ATPase were studied in control and hypoxic isolated rat hearts. The control hearts were perfused with medium gassed with 95% O2 and 5% CO2, whereas hypoxia was induced by perfusing the hearts with medium gassed with 95% N2 and 5% CO2. The specific activity of the Na+–K+ ATPase was lower in the hypoxic hearts than in the control preparations. The enzyme activity of the hypoxic hearts was also lower when determined under different assay conditions obtained by changing the concentration of Na+, K+, H+, and MgATP in the incubation medium. The ouabain-induced inhibition of Na+–K+ ATPase activity in the hypoxic hearts was similar to that in the control. The depression in Na+–K+ ATPase activity due to hypoxia was reversible on perfusing the hypoxic heart with aerobic medium. The decreased Na+–K+ ATPase activity in the hypoxic heart preparations supports the concept of membrane abnormality associated with heart failure due to lack of oxygen. Since the depression in the activity of Na+–K+ ATPase in the hypoxic heart was markedly pronounced on omitting the substrate from the perfusion medium, it is likely that exogenous glucose plays an important role in maintaining the integrity of hypoxic heart membranes.