Changes in nitric oxide and free radical levels in rat gastrocnemius muscle during contraction and fatigue.

1. The ratio of nitric oxide (NO) to free radicals is critical during skeletal muscle contraction. Changes in this ratio have been suggested to play a role in muscle fatigue. 2. The aim of the present study was to investigate the changes in NO and free radicals during tetanic and subtetanic contraction and fatigue in the gastrocnemius muscle of adult male Wistar rats. 3. Rats were subjected to either low- or high-frequency stimulation (10 and 100 Hz, respectively) of the right gastrocnemius muscle. Both groups were further subdivided into untreated (0.9% NaCl solution), N(G) -nitro-L-arginine methyl ester (L-NAME)-treated and reduced glutathione (GSH)-treated groups. Rats were administered their treatments intraperitoneally 30 min prior to electrical stimulation. 4. Levels of both NO and lipid peroxides increased significantly during peak force contraction for either type of contractions, with a more significant response during subtetanic contraction. Treatment with L-NAME significantly reduced the maximal force and this effect was more marked in the low frequency-stimulated group. Although peroxides levels were reduced by GSH, it had no significant effect on force production. In L-NAME-treated rats, the onset of 50% fatigue was accelerated with a significant increase in peroxides levels, whereas the opposite effects were observed after GSH treatment. 5. Current results reflect the importance of endogenous NO, as an anti-oxidant, in aiding muscle performance by overcoming oxidative stress during fatigue. They provide a possible explanation as to why patients with myopathies like Duchenne muscular dystrophy, in which dystrophin is lacking suffer from muscle weakness and fatigue easily.