Nitric oxide release and contractile properties of skeletal muscles from mice deficient in type IIINOS

Skeletal muscle constitutively expresses both the type I(neuronal) and type III (endothelial) isoforms of nitric oxide synthase (NOS). We tested the f unctional importance of type III NOS using skeletal muscles with similar le vels of type III NOS expression (diaphragm and soleus) from wild-type, hete rozygous, and type III NOS-deficient littermate mice. Muscles were incubate d at 37 degrees C in Krebs-Ringer solution. NO accumulation in the medium w as measured by chemiluminescence; force-frequency and fatigue characteristi cs were measured using direct electrical stimulation. Diaphragm and soleus released NO at similar rates during passive incubation; these rates increas ed during active contraction. NO release by type III NOS-deficient muscle w as not different from that of wild-type muscle under any condition tested. Force-frequency and fatigue characteristics also were unaffected by genotyp e. Because type III NOS deficiency did not alter function, we conclude that NO effects previously observed in wild-type muscle are likely to be mediat ed by type I NOS.