Histological determination of nitric oxide synthase (NOS) and NADPH-diaphorase in ragged-red fibers from patients with mitochondrial encephalomyopathies.

To determine localization of nitric oxide synthase in diseased muscle, we performed immunohistochemical analyses of neuronal-type nitric oxide synthase (nNOS) and endothelial-type nitric oxide synthase (ec-NOS) in biopsied muscles from five patients with mitochondrial encephalomyopathies. Immunostaining of nNOS was prominent in the sarcolemmal region of the ragged-red fibers, and weak in the sarcolemmal region of normal fibers. Immunostaining of ec-NOS was strongly positive in the myofibrils of ragged-red fibers. Ec-NOS immunoreactivity corresponded to fibers positive for SDH by histochemistry. Histochemical methods revealed prominent staining for NADPH-diaphorase on surface membranes of the ragged-red fibers. Findings suggest that nitric oxide is important in the muscles of patients with mitochondrial encephalomyopathies.