Muscle-derived nitric oxide synthase expression, differences associated with muscle fiber-type, and disease susceptibility in a rat model of myasthenia gravis

Reports from this laboratory suggested that expression of skeletal muscle-derived, inducible nitric oxide synthase (iNOS), is associated with resistance of a particular rat strain to the autoimmune model of myasthenia gravis (MG). The study reported below demonstrates a similar association between iNOS induction in skeletal muscle and disease-resistance when comparing different skeletal muscles originating from the same rat strain. Thus, soleus muscles, shown previously to be relatively resistant to disease even when obtained from disease-susceptible Lewis rats, were observed to express high levels of iNOS following exposure to antibody reactive with the nicotinic acetylcholine receptor (AChR). Increased iNOS expression appears to be associated with slow-twitch, type 1 fibers and would explain the relatively high iNOS expression in soleus muscles since they are dominated by this fiber type, compared to disease-susceptible EDL muscles which are dominated by fast-twitch, type 2 fibers.