Induction of neuronal type nitric oxide synthase in skeletal muscle by chronic electrical stimulation in vivo.

Fast-twitch skeletal muscles contain more neuronal-type nitric oxide synthase (nNOS) than slow-twitch muscles because nNOS is present only in fast (type II) muscle fibers. Chronic in vivo electrical stimulation of tibialis anterior and extensor digitorum longus muscles of rabbits was used as a method of inducing fast-to-slow fiber type transformation. We have studied whether an increase in muscle contractile activity induced by electrical stimulation alters nNOS expression, and if so, whether the nNOS expression decreases to the levels present in slow muscles. Changes in the expression of myosin heavy chain isoforms and maximum velocity of shortening of skinned fibers indicated characteristic fast-to-slow fiber type transformation after 3 wk of stimulation. At the same time, activity of NOS doubled in the stimulated muscles, and this correlated with an increase in the expression of nNOS shown by immunoblot analysis. These data suggest that nNOS expression in skeletal muscle is regulated by muscle activity and that this regulation does not necessarily follow the fast-twitch and slow-twitch pattern during the dynamic phase of phenotype transformation.