Nitric oxide synthase inhibitors reduce sarcomere addition in rat skeletalmuscle

1. Mechanical stimuli are thought to modulate the number of sarcomeres in s eries (sarcomere number) in skeletal muscle fibres. However, the mechanisms by which muscle cells transduce mechanical signals into serial sarcomere a ddition have not been explored. In this study, we test the hypothesis that nitric oxide positively modulates sarcomere addition. 2. The soleus muscle was cast-immobilized in a shortened position in 3-week -old female Wistar rats. After 4 weeks, the casts were removed, creating a period of rapid sarcomere addition. During the remobilization period, nitri c oxide synthase (NOS) inhibitors or substrate were administered. 3. Rats treated with the non-isoform-specific NOS inhibitor L-nitro-arginin e methyl ester during 3 weeks of remobilization had smaller soleus sarcomer e numbers than control rats. Rats treated with 1-(2- trifluoromet-phenyl )- imidazole, which has greater specificity for the neuronal isoform than for the endothelial isoform of NOS, also had smaller soleus sarcomere numbers t han control rats. These results suggest that inhibition of the neuronal iso form of NOS reduces sarcomere addition during remobilization. 4. Rats treated with L-arginine, the substrate for NOS, during 1 week of re mobilization had soleus sarcomere numbers for the immobilized-remobilized m uscle which were closer to that for the contralateral, non-immobilized musc le than did rats that were not treated with L-arginine, 5. These results support the hypothesis that nitric oxide derived from the neuronal isoform of NOS positively modulates sarcomere addition.