UC San Diego

Nitric oxide (NO) is an important signaling molecule in the process of muscle repair. It is involved in inflammatory signaling as well as satellite cell signaling– specifically satellite cell proliferation, differentiation and maturation. Previous studies have shown that NO impacts exercise performance and fatigue resistance, but there are less studies on the impact of NO after exercise, during muscle repair. We investigated the role that nitric oxide modulation may play in muscle repair with a GSNOR inhibitor (SPL-334), ISDN (isosorbide dinitrate–NO donor), and L-NIL (iNOS inhibitor). We found that GSNORi attenuated reduction of force after exercise-induced muscle damage (EIMD) in a lengthening-contractions model in EDL (extensor digitorum longus) muscle but did not affect the number of Tdt+ myofibers or cross-sectional area of the Tdt+ myofibers in the TA (tibialis anterior) muscle. ISDN had no effect on force production but decreased the number of Tdt+ myofibers and increased the CSA (cross-sectional area) of Tdt+ myofibers. L-NIL did not affect the force reduction but did increase the total number of Tdt+ myofibers post-EIMD. These data suggest that excess NO via ISDN may reduce quiescent satellite cell activation, iNOS inhibition may increase regeneration via macrophage signaling, and GSNORi may not impact muscle regeneration but instead affect the force produced post-LCP via ryanodine receptor hypernitrosylation.