Inhibition of NADPH Oxidase May Promote Exercise Endurance

Repetitive muscle contraction is associated with increased superoxide production in skeletal muscle. 1-8 There is considerable evidence that muscle fatigue during prolonged exercise is associated with oxidant stress in muscle fibers, and that this stress is indeed partially responsible for the fatigue. Thus, pharmacological strategies which depress the antioxidant defenses of muscle fibers accelerate the onset of fatigue, whereas certain agents which scavenge oxidants, such as N-acetylcysteine and pegylated superoxide dismutase, have been shown to postpone muscle fatigue in vivo and in isolated muscle preparations. 1;2;6 Peroxynitrite may be a prominent mediator of this muscle dysfunction, inasmuch as muscle fibers also produce nitric oxide. 4;8;9 While it is still unclear which targets of oxidant stress are the primary mediators of oxidant-induced fatigue, studies indicate that function of the sarcoplasmic reticulum (the calcium release channel and the calcium-ATPase), of the plasma membrane Na + /K + -ATPase, and of mitochondria can be disrupted by excessive oxidant exposure. 1