Superoxide, hydroxyl radical, and hydrogen peroxide effects on single-diaphragm fiber contractile apparatus

• Published in: Journal of applied physiology (1985) Vol. 90; no. 1; pp. 45 - 54
• Main Authors: Callahan, L. A, She, Z. W, Nosek, T. M
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01-01-2001; American Physiological Society
• Subjects: Air breathing; Animals; Biological and medical sciences; Diaphragm - physiology; Effects; Fundamental and applied biological sciences. Psychology; Hydrogen; Hydrogen Peroxide - pharmacology; Hydroxyl Radical - pharmacology; Muscle Contraction - drug effects; Muscle Fibers, Skeletal - physiology; Muscular system; Osmolar Concentration; Oxygen; Rats; Rats, Sprague-Dawley; Respiratory system; Respiratory system: anatomy, metabolism, gas exchange, ventilatory mechanics, respiratory hemodynamics; Superoxides - pharmacology; Vertebrates: respiratory system; Calcium; Rat; Rodentia; Contractility; Hydrogen Peroxides; Free radical; Vertebrata; Hyperoxides; Sensitivity; Mammalia; Respiratory muscle; Radical anion; Diaphragm; Hydroxyl
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.2001.90.1.45

1  Division of Pulmonary and Critical Care Medicine,
Department of Medicine, and 3  Department of Physiology and
Biophysics, Case Western Reserve University, Cleveland, Ohio 44109; and
2  Department of Medicine, Medical College of Georgia, Augusta,
Georgia 30912
Reactive oxygen
species contribute to diaphragm dysfunction in certain
pathophysiological conditions (i.e., sepsis and fatigue). However, the precise alterations induced by reactive oxygen species or
the specific species that are responsible for the derangements in
skeletal muscle function are incompletely understood. In this study, we
evaluated the effect of the superoxide anion radical (O 2 ·), hydroxyl radical (·OH), and hydrogen
peroxide (H 2 O 2 ) on maximum calcium-activated
force (F max ) and calcium sensitivity of the contractile
apparatus in chemically skinned (Triton X-100) single rat diaphragm
fibers. O 2 · was generated using the
xanthine/xanthine oxidase system; ·OH was generated using 1 mM
FeCl 2 , 1 mM ascorbate, and 1 mM
H 2 O 2 ; and H 2 O 2 was
added directly to the bathing medium. Exposure to O 2 · or ·OH significantly decreased
F max by 14.5% ( P  < 0.05) and 43.9%
( P  < 0.005), respectively. ·OH had no effect on
Ca 2+ sensitivity. Neither 10 nor 1,000 µM
H 2 O 2 significantly altered F max or
Ca 2+ sensitivity. We conclude that the diaphragm is
susceptible to alterations induced by a direct effect of ·OH and
O 2 ·, but not H 2 O 2 , on the
contractile proteins, which could, in part, be responsible for
prolonged depression in contractility associated with respiratory
muscle dysfunction in certain pathophysiological conditions.
free radicals; reactive oxygen species; skinned muscle fibers; respiratory muscle; skeletal muscle