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Nitric oxide in skeletal muscle

Nature volume 372, pages 546–548 (1994)Cite this article

Abstract

REACTIVE oxygen intermediates modulate skeletal muscle contraction1,2, but little is known about the role of nitric oxide (NO). Here we show that rat skeletal muscle expresses neuronal-type NO synthase and that activity varies among several respiratory and limb muscles. Immunohistochemistry showed prominent staining of type II (fast) fibre cell membranes with antibodies against neuronal-type NO synthase. NO synthase activity in muscles correlated with type II fibre density. Resting diaphragm muscle produced detectable NOx, but no reactive oxygen intermediates. In contrast, actively contracting muscle generated increased levels of reactive oxygen intermediates. Contractile function was augmented by blockers of NO synthase, extracellular NO chela-tion, and guanylyl cyclase inhibition; it was depressed by NO donors and by increased levels of cyclic GMP. Force–frequency plots of different muscles showed an inverse correlation between NO synthase activity and force development. Our results support two physiological functions of NO in skeletal muscle. The first is to promote relaxation through the cGMP pathway3,4. The second is to modulate increases in contraction that are dependent on reactive oxygen intermediates and which are thought to occur through reactions with regulatory thiols on the sarcoplasmic reticulum5,6.

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Authors and Affiliations

  1. Department of Pathology, Brigham and Women's Hospital and Physiology Program, Harvard School of Public Health, Boston, Massachusetts, 02115, USA

    Lester Kobzik

  2. Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, Texas, 77030, USA

    Michael B. Reid

  3. Department of Physiology, UCSF, San Francisco, California, 94143, USA

    David S. Bredt

  4. Department of Medicine, Pulmonary and Cardiovascular Divisions, and Department of Cell Biology, Duke University Medical Center, Box 3177, Durham, North-Carolina, 27710, USA

    Jonathan S. Stamler

Authors
  1. Lester Kobzik
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  2. Michael B. Reid
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  3. David S. Bredt
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  4. Jonathan S. Stamler
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Kobzik, L., Reid, M., Bredt, D. et al. Nitric oxide in skeletal muscle. Nature 372, 546–548 (1994). https://doi.org/10.1038/372546a0

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