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Am J Physiol Lung Cell Mol Physiol 281: L1402-L1412, 2001;
1040-0605/01 $5.00
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Vol. 281, Issue 6, L1402-L1412, December 2001

Free radicals in hypoxic rat diaphragm contractility: no role for xanthine oxidase

Leo M. A. Heunks1, Herwin A. Machiels1, Ronney de Abreu2, Xiao Ping Zhu1, Henricus F. M. van der Heijden1, and P. N. Richard Dekhuijzen1

1 Department of Pulmonary Diseases and 2 Department of Paediatrics, University Medical Centre Nijmegen, 6500 HB Nijmegen, The Netherlands

Recent evidence indicates that hypoxia enhances the generation of oxidants. Little is known about the role of free radicals in contractility of the rat diaphragm during hypoxia. We hypothesized that antioxidants improve contractility of the hypoxic rat diaphragm and that xanthine oxidase (XO) is an important source of free radicals in the hypoxic diaphragm. The effects of N-acetylcysteine (NAC; 18 mM), Tiron (10 mM), and the XO inhibitor allopurinol (250 µM) were studied on isometric and isotonic force generation during hypoxia (PO2 ~7 kPa). NAC and Tiron decreased maximal force generation, slowed the shortening velocity, and decreased the power output. Fatigue rate was decreased in the presence of either NAC or Tiron. Allopurinol did not alter the contractility or fatigability of the diaphragm. During hyperoxia (PO2 ~85 kPa), neither NAC nor allopurinol affected the contractility or fatigability of the diaphragm. Thus free radicals play a significant role in diaphragm contractility during hypoxia. Whether antioxidants exert a beneficial or harmful effect on muscle performance depends on the contraction pattern of the muscle. Free radicals generated by XO do not play a role in diaphragm contractility during either hypoxia or hyperoxia.

isotonic contractions; allopurinol; Tiron; N-acetylcysteine; respiratory muscles


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