Prevention of muscle fibers atrophy during gravitational unloading: The effect of l-arginine administration

Gravitational unloading results in pronounced atrophy of m.soleus. Probably, the output of NO is controlled by the muscle activity. We hypothesized that NO may be involved in the protein metabolism and increase of its concentration in muscle can prevent atrophic changes induced by gravitational unloading. In order to test the hypothesis we applied NO donor l-arginine during gravitational unloading. 2.5-month-old male Wistar rats weighing 220–230g were divided into sedentary control group (CTR, n=7), 14-day hindlimb suspension (HS, n=7), 14 days of hindlimb suspension+l-arginine (HSL, n=7) (with a daily supplementation of 500 mg/kg wt l-arginine) and 14 days of hindlimb suspension+l-NAME (HSN, n=7) (90 mg/kg wt during 14 days). Cross sectional area (CSA) of slow twitch (ST) and fast twitch (FT) soleus muscle fibers decreased by 45% and 28% in the HS group (p<0.05) and 40% and 25% in the HSN group, as compared to the CTR group (p<0.05), respectively. CSA of ST and FT muscle fibers were 25% and 16% larger in the HSL group in comparison with the HS group (p<0.05), respectively. The atrophy of FT muscle fibers in the HSL group was completely prevented since FT fiber CSA had no significant differences from the CTR group. In HS group, the percentage of fibers revealing either gaps/disruption of the dystrophin layer of the myofiber surface membrane increased by 27% and 17%, respectively, as compared to the controls (CTR group, p<0.05). The destructions in dystrophin layer integrity and reductions of desmin content were significantly prevented in HSL group. NO concentration decreased by 60% in the HS group (as well as HSN group) and at the same time no changes were detectable in the HSL group. This fact indicates the compensation of NO content in the unloaded muscle under l-arginine administration. The levels of atrogin-1 mRNA were considerably altered in suspended animals (HS group: plus 27%, HSL group: minus 13%) as compared to the control level. Conclusion: l-arginine administration allows maintaining NO concentration in m.soleus at the level of cage control group, prevents from dystrophin layer destruction, decreases the atrogin mRNA concentration in the muscle and atrophy level under gravitational unloading.