Abstract 12803: Nitric Oxide is Involved the Beneficial Effects of Exercise Training via Activating Skeletal Muscle Mitochondrial Biogenesis in Mice
Background: Exercise training (ET) enhances mitochondria function in the skeletal muscle and increases the exercise capacity. Resent study has reported that nitric oxide (NO) regulates the gene expression involved in the mitochondrial biogenesis. However, it remains unknown whether NO plays a central role in these effects by ET. Therefore, we investigated the effects of chronic administration N-ω-nitro-L-arginine methyl ester (L-NAME), a NO synthase (NOS) inhibitor, on ET-induced skeletal muscle adaptation in mice.
Methods: Male C57BL/6J mice were divided into 4 groups of mice (n = 12 per group); sedentary (SED), SED+L-NAME, ET and ET+L-NAME. L-NAME was administered in the drinking water (1 mg/mL), and ET was performed by swimming (90 min/day, 5 days/week). After 5 weeks, treadmill tests with expired gas analysis were performed to measure the work and oxygen uptake (VO2). The enzymatic activity of citrate synthase and mitochondrial complex I and III as well as gene expression regulating mitochondrial biogenesis such as peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and mitochondrial transcription factor A (Tfam) were measured in the skeletal muscle.
Results: The work and peak VO2 were significantly increased in ET compared to SED (work; 30.8 ± 0.5 vs. 26.5 ± 0.3 J and peak VO2; 170 ± 2 vs. 151 ± 2 ml/kg/min, respectively p<0.05), and these increases were completely inhibited in ET+L-NAME (work; 26.1 ± 0.4 J and peak VO2; 152 ± 1 ml/kg/min). ET significantly increased the activities of citrate synthase and mitochondrial complex I and III, and gene expression of PGC-1α and Tfam, which were completely inhibited by the treatment with L-NAME. However, these effects of L-NAME were not observed in SED groups. Moreover, the administration of L-arginine (50 mg/ml) to ET+L-NAME significantly increased exercise capacity and mitochondrial function in the skeletal muscle.
Conclusion: The inhibition of NOS inhibited the increase in exercise capacity and the enhancement of mitochondrial function in the skeletal muscle induced by ET, which was canceled by L-arginine. Thus, NO is involved in the beneficial effects possibly via activating mitochondrial biogenesis.
- © 2011 by American Heart Association, Inc.