Concerted regulation of skeletal muscle contractility by oxygen tension and endogenous nitric oxide.

Journal Article (Journal Article)

It is generally accepted that inhibition of nitric oxide synthase (NOS) facilitates, and thus nitric oxide (NO) inhibits, contractility of skeletal muscle. However, standard assessments of contractility are carried out at a nonphysiological oxygen tension [partial pressure of oxygen (pO2)] that can interfere with NO signaling (95% O2). We therefore examined, in normal and neuronal NOS (nNOS)-deficient mice, the influence of pO2 on whole-muscle contractility and on myocyte calcium flux and sarcomere shortening. Here, we demonstrate a significant enhancement of these measures of muscle performance at low physiological pO2 and an inhibitory influence at higher physiological pO2, which depend on endogenous nNOS. At 95% O2 (which produces oxidative stress; muscle core pO2 approximately 400 mmHg), force production is enhanced but control of contractility by NO/nitrosylation is greatly attenuated. In addition, responsivity to pO2 is altered significantly in nNOS mutant muscle. These results reveal a fundamental role for the concerted action of NO and O2 in physiological regulation of skeletal muscle contractility, and suggest novel molecular aspects of myopathic disease. They suggest further that the role of NO in some cellular systems may require reexamination.

Full Text

Duke Authors

Cited Authors

  • Eu, JP; Hare, JM; Hess, DT; Skaf, M; Sun, J; Cardenas-Navina, I; Sun, Q-A; Dewhirst, M; Meissner, G; Stamler, JS

Published Date

  • December 9, 2003

Published In

Volume / Issue

  • 100 / 25

Start / End Page

  • 15229 - 15234

PubMed ID

  • 14645704

Pubmed Central ID

  • PMC299968

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.2433468100


  • eng

Conference Location

  • United States