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

Leo M.A. Heunks, Herwin A. Machiels, Ronney De Abreu, Xiao Ping Zhu, Henricus F.M. Van Der Heijden, P. N.Richard Dekhuijzen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number6 25-6
Publication statusPublished - 31 Dec 2001

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