RELATIONSHIP OF OXYPURINE RELEASE TO CONTRACTILE FAILURE IN DINITROPHENOL-TREATED RAT SKELETAL-MUSCLE

The efflux of hypoxanthine and uric acid from skeletal muscle has been noted to follow exercise and metabolic stress both in vivo and in vit ro. Since the action of xanthine oxidase and hypoxanthine generates fr ee radicals with potential damaging effect on the muscle membranes, an in vitro model was used to study the relationship of metabolic stress , oxypurine release and muscle contraction. When rat epitrochlearis mu scle was exposed to the mitochondrial uncoupler dinitrophenol at 37-de grees-C, lactate release was pronounced and hypoxanthine and uric acid appeared in the incubating medium. The twitch tension, in response to supramaximal stimulation, was reduced to less than 5% of the initial value. When the same experiment was repeated at 27-degrees-C, hypoxant hine and uric acid formation was inhibited, although lactate release i ndicated that metabolic stress was still present. Twitch tension was r elatively preserved (57% of the initial value). The lower temperature did not alter the decrease in ATP and phosphocreatine levels in the mu scle which is produced by dinitrophenol. There was an inverse relation ship between oxypurine release and twitch tension in individual muscle s (r = 0.80, P < 0.01 for hypoxanthine and r = 0.95, P < 0.0002 for ur ic acid). Xanthine dehydrogenase/xanthine oxidase was detected in musc le and between 16 and 22% of the activity was in the oxidase form.