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PMID: 9844020 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 25 ·1998-12-08 ·Pages 15090-5

Thomas GD, Sander M, Lau KS, Huang PL, Stull JT, Victor RG

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 alpha-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 alpha-adrenergic vasoconstriction in active skeletal muscle.

MeSH Terms
Animals Dystrophin/deficiency Male Mice Mice, Inbred C57BL Muscle, Skeletal/blood supply,physiopathology Muscular Dystrophy, Animal/physiopathology Receptors, Adrenergic, alpha/physiology Vasoconstriction/physiology
Chemicals
Dystrophin Receptors, Adrenergic, alpha
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Thomas G D
Department of Internal Medicine, Hypertension Division, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235, USA. gthom1@mednet.swmed.edu
Sander M
Lau K S
Huang P L
Stull J T
Victor R G
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.25.15090
Email
gthom1@mednet.swmed.edu
Published
1998-12-08
Pages
15090-5
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24580
Subset
IM
Grants
NHLBI NIH HHS · P01 HL006296 · United States
NHLBI NIH HHS · P01-HL-06296 · United States
Corrections
CommentIn
PMID: 9843933
External Links
PubMed source DOI: 10.1073/pnas.95.25.15090 PMC Full Text View journal details
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