Effect of xanthine oxidase-generated extracellular superoxide on skeletal muscle force generation

peroxide on skeletal muscle force generation. Am J Physiol Regul Integr Comp Physiol 298: R2–R8, 2010. First published October 14, 2009; doi:10.1152/ajpregu.00142.2009.—Skeletal muscle contrac-tions increase superoxide anion in skeletal muscle extracellular space. We tested the hypotheses that 1) after an isometric contraction protocol, xanthine oxidase (XO) activity is a source of superoxide anion in the extracellular space of skeletal muscle and 2) the increase in XO-derived extracellular superoxide anion during contractions affects skeletal muscle contractile function. Superoxide anion was monitored in the extracellular space of mouse gastrocnemius muscles by following the reduction of cytochrome c in muscle microdialysates. A 15-min protocol of nondamaging isometric contractions increased the reduction of cytochrome c in microdialysates, indicating an increase in superoxide anion. Mice treated with the XO inhibitor oxypurinol showed a smaller increase in superoxide anions in muscl