The major isoform of nitric oxide synthase (NOS) in skeletal muscle is the splice variant of neuronal NOS, termed nNOS. Exercise training increases nNOS protein levels in rat skeletal muscle, but data in humans are conflicting. We performed two studies to determine 1) whether resting nNOS protein expression is greater in skeletal muscle of 10 endurance-trained athletes compared with 11 sedentary individuals (study 1) and 2) whether intense short-term (10 days) exercise training increases

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... nNOS protein (within whole muscle and also within types I, IIa, and IIx fibers) in eight sedentary individuals (study 2). In study 1, nNOS protein was ϳ60% higher (P Ͻ 0.05) in endurance-trained athletes compared with the sedentary participants. In study 2, nNOS protein expression was similar in types I, IIa, and IIx fibers before training. Ten days of intense exercise training significantly (P Ͻ 0.05) increased nNOS protein levels in types I, IIa, and IIx fibers, a finding that was validated by using whole muscle samples. Endothelial NOS and inducible NOS protein were barely detectable in the skeletal muscle samples. In conclusion, nNOS protein expression is greater in endurance-trained individuals when compared with sedentary individuals. Ten days of intense exercise is also sufficient to increase nNOS expression in untrained individuals, due to uniform increases of nNOS within types I, IIa, and IIx fibers.