title: Impaired metabolic modulation of alpha-adrenergic vasoconstriction in dystrophin-deficient skeletal muscle.
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.
authors.affiliation: Department of Internal Medicine, Hypertension Division, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235, USA. gthom1@mednet.swmed.edu
authors.forename: G D
authors.initials: GD
authors.lastname: Thomas
authors.forename: M
authors.initials: M
authors.lastname: Sander
authors.forename: K S
authors.initials: KS
authors.lastname: Lau
authors.forename: P L
authors.initials: PL
authors.lastname: Huang
authors.forename: J T
authors.initials: JT
authors.lastname: Stull
authors.forename: R G
authors.initials: RG
authors.lastname: Victor
mesh_terms: D000818:Animals; D016189:Dystrophin / Q000172:deficiency*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000503:physiopathology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D016189:Dystrophin; D011942:Receptors, Adrenergic, alpha