Antioxidative defence alterations in skeletal muscle during prolonged acclimation to cold: role of L-arginine/NO-producing pathway.

Early in cold acclimation (1-7 days), heat is produced by shivering, while late in cold acclimation (12-45 days), skeletal muscle contributes to thermogenesis by tissue metabolism other than contractions. Given that both thermogenic phases augment skeletal muscle aerobic power and reactive species production, we aimed in this study to examine possible changes in skeletal muscle antioxidative defence (AD) during early and late cold acclimation with special emphasis on the influence of the L-arginine/nitric oxide (NO)-producing pathway on the modulation of AD in this tissue. Adult Mill Hill hybrid hooded rat males were divided into two main groups: a control group, which was kept at room temperature (22+/-1 degrees C), and a group maintained at 4+/-1 degrees C for 45 days. The cold-acclimated group was divided into three subgroups: untreated, L-arginine treated and N(omega)-nitro-L-arginine methyl ester (L-NAME) treated. The AD parameters were determined in the gastrocnemius muscle on day 1, 3, 7, 12, 21 and 45 of cold acclimation. The results showed an improvement of skeletal muscle AD in both early and late cold acclimation. Clear phase-dependent changes were seen only in copper, zinc superoxide dismutase activity, which was increased in early cold acclimation but returned to the control level in late acclimation. In contrast, there were no phase-dependent changes in manganese superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, the activities of which were increased during the whole cold exposure, indicating their engagement in both thermogenic phases. L-Arginine in early cold acclimation accelerated the cold-induced AD response, while in the late phase it sustained increases achieved in the early period. L-NAME affected both early and late acclimation through attenuation and a decrease in the AD response. These data strongly suggest the involvement of the L-arginine/NO pathway in the modulation of skeletal muscle AD.