Impaired metabolic modulation of α-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle

Gail D. Thomas, Mikael Sander, Kim S. Lau, Paul L. Huang, James T. Stull, Ronald G. Victor

Research output: Contribution to journalArticle

305 Citations (Scopus)

Abstract

The neuronal isoform of nitric oxide synthase (nNOS) is highly expressed in mammalian skeletal muscle, but its functional role has not been defined. NO has been implicated in the local metabolic regulation of blood flow in contracting skeletal muscle in part by antagonizing sympathetic vasoconstriction. We therefore hypothesized that nNOS in skeletal muscle is the source of the NO mediating the inhibition of sympathetic vasoconstriction in contracting muscle. In the mdx mouse, a model of Duchenne muscular dystrophy in which dystrophin deficiency results in greatly reduced expression of nNOS in skeletal muscle, we found that the normal ability of skeletal muscle contraction to attenuate α-adrenergic vasoconstriction is defective. Similar results were obtained in mutant mice that lack the gene encoding nNOS. Together these data suggest a specific role for nNOS in the local metabolic inhibition of α-adrenergic vasoconstriction in active skeletal muscle.

Original languageEnglish (US)
Pages (from-to)15090-15095
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number25
DOIs
StatePublished - Dec 8 1998

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Dystrophin
Nitric Oxide Synthase Type I
Vasoconstriction
Adrenergic Agents
Skeletal Muscle
Protein Isoforms
Inbred mdx Mouse
Duchenne Muscular Dystrophy
Muscle Contraction
Muscles
Genes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Impaired metabolic modulation of α-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle. / Thomas, Gail D.; Sander, Mikael; Lau, Kim S.; Huang, Paul L.; Stull, James T.; Victor, Ronald G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 25, 08.12.1998, p. 15090-15095.

Research output: Contribution to journalArticle

Thomas, Gail D. ; Sander, Mikael ; Lau, Kim S. ; Huang, Paul L. ; Stull, James T. ; Victor, Ronald G. / Impaired metabolic modulation of α-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 25. pp. 15090-15095.
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