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Nitric oxide synthase expression and effects of nitric oxide modulation on contractility of rat extraocular muscle

CHELLIAH R. RICHMONDS^* and HENRY J. KAMINSKI¹

Departments of
^* Neurology and
Neurosciences, Case Western Reserve University School of Medicine, Louis Stokes Cleveland Veterans Affairs Medical Center, University Hospitals of Cleveland, Cleveland, Ohio 44106, USA

¹Correspondence: Department of Neurology, University Hospitals of Cleveland, 11100 Euclid Ave., Cleveland, OH, 44106, USA. E-mail: hjk3{at}po.cwru.edu

Extraocular muscles (EOMs) are specialized skeletal muscles that are constantly active, generate low levels of force for cross sectional area, have rapid contractile speeds, and are highly fatigue resistant. The neuronal isoform of nitric oxide synthase (nNOS) is concentrated at the sarcolemma of fast-twitch muscles fibers, and nitric oxide (NO) modulates contractility. This study evaluated nNOS expression in EOM and the effect of NO modulation on lateral rectus muscle’s contractility. nNOS activity was highest in EOM compared with diaphragm, extensor digitorum longus, and soleus. Neuronal NOS was concentrated to the sarcolemma of orbital and global singly innervated fibers, but not evident in the multi-innervated fibers. The N^G-nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor), increased submaximal tetanic and peak twitch forces. The NO donors S-nitroso-N-acetylcysteine (SNAC) and spermineNONOate reduced submaximal tetanic and peak twitch forces. The effect of NO on the contractile force of lateral rectus muscle is greater than previously observed on other skeletal muscle. NO appears more important in modulating contraction of EOM compared with other skeletal muscles, which could be important for the EOM’s specialized role in generation of eye movements.—Richmonds, C. R., Kaminski, H. J. Nitric oxide synthase expression and effects of nitric oxide modulation on contractility of rat extraocular muscle.

Key Words: extraocular muscle • nitric oxide • muscle contractility • neuronal nitric oxide synthase

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