INHIBITION OF CARDIAC SARCOLEMMA NA-K+ ATPASE BY OXYRADICAL GENERATING SYSTEMS()

The Na+-K(+)ATPase activity and SH group content were decreased wherea s malondialdehyde (MDA) content was increased upon treating the porcin e cardiac sarcolemma with xanthine plus xanthine oxidase, which is kno wn to generate superoxide and other oxyradicals. Superoxide dismutase either alone or in combination with catalase and mannitol fully preven ted changes in SH group content but the xanthine plus xanthine oxidase -induced depression in Na+-K(+)ATPase activity as well as increase in MDA content were prevented partially. The Lineweaver-Burk plot analysi s of the data for Na+-K(+)ATPase activity in the presence of different concentrations of MgATP or Na+ revealed that the xanthine plus xanthi ne oxidase-induced depression in the enzyme activity was associated wi th a decrease in V-max and an increase in K-m for MgATP; however, K-a value for Na+ was decreased. Treatment of sarcolemma with H2O2 plus Fe 2+, an hydroxyl and other radical generating system, increased MDA con tent but decreased both Na+-K(+)ATPase activity and SH group content; mannitol alone or in combination with catalase prevented changes in SH group content fully but the depression in Na+-K(+)ATPase activity and increase in MDA content were prevented partially The depression in th e enzyme activity by H2O2 plus Fe2+ was associated with a decrease in V-max and an increase in K-m for MgATP. These results indicate that th e depressant effect of xanthine plus xanthine oxidase on sarcolemmal N a+-K(+)ATPase may be due to the formation of superoxide, hydroxyl and other radicals. Furthermore, the oxyradical-induced depression in Na+- K(+)ATPase activity may be due to a decrease in the affinity of substr ate in the sarcolemmal membrane.