Nitric oxide in skeletal muscle

Inhibition of nitric oxide synthase inhibits walking speed in rats

Min Xia Wang, Dédée F. Murrell, Csaba Szabo, Russell F. Warren, Maria Sarris, George A C Murrell

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Nitric oxide (NO·) is a multifunctional messenger molecule generated by a family of enzymes called the nitric oxide synthases (NOSs). Although NOSs have been identified in skeletal muscle, specifically brain NOS (bNOS) and endothelial NOS (eNOS), their role has not been well clarified. The goals of this investigation were to (1) characterize the immunoreactivity, Ca 2+ dependence, and activity of NOS in human and rat skeletal muscle and (2) using a rat model, investigate the effect of chronic blockade of NOS on skeletal muscle structure and function. Our results showed that both human and rodent skeletal muscle had NOS activity. This NOS activity was similar to that of the endothelial and brain NOS isoforms in that it was calcium-dependent. However, Western blot analysis consistently showed that a polyclonal antibody raised against a peptide sequence of human inducible NOS (iNOS) reacted with a protein with a molecular weight (95 kDa) that was different from that of other NOS isoforms. RT-PCR analysis identified the mRNA expression of not only eNOS and bNOS but also iNOS in human and rat muscle. Inhibition of nitric oxide synthase in rats with N w-nitro-L-arginine methyl ester (L-NAME) resulted in a progressive, severe reduction in walking speed (30-fold reduction in walking velocity at day 22, P < 0.001), muscle fiber cross-sectional area (40% reduction at day 22, P < 0.001), and muscle mass (40% reduction in dry weight at day 22, P < 0.01). Rats fed the same regimen of the enantiomer of L-NAME (D-NAME) had normal motor function, muscle fiber morphology, and muscle mass. Taken together, these results imply that there may be a novel nitric oxide synthase in muscle and that NO· generated from muscle may be important in muscle function.

Original languageEnglish (US)
Pages (from-to)219-232
Number of pages14
JournalNitric Oxide - Biology and Chemistry
Volume5
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Nitric Oxide Synthase
Muscle
Rats
Nitric Oxide
Skeletal Muscle
Muscles
Nitric Oxide Synthase Type III
NG-Nitroarginine Methyl Ester
Brain
Protein Isoforms
Walking Speed
Nitric Oxide Synthase Type II
Arginine
Enantiomers
Fibers
Nitric oxide
Walking
Rodentia
Molecular Weight
Western Blotting

Keywords

  • Free radical
  • Human muscle
  • Muscle-NOS
  • Nitric oxide
  • Nitric oxide synthase
  • Skeletal muscle

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Nitric oxide in skeletal muscle : Inhibition of nitric oxide synthase inhibits walking speed in rats. / Wang, Min Xia; Murrell, Dédée F.; Szabo, Csaba; Warren, Russell F.; Sarris, Maria; Murrell, George A C.

In: Nitric Oxide - Biology and Chemistry, Vol. 5, No. 3, 2001, p. 219-232.

Research output: Contribution to journalArticle

Wang, Min Xia ; Murrell, Dédée F. ; Szabo, Csaba ; Warren, Russell F. ; Sarris, Maria ; Murrell, George A C. / Nitric oxide in skeletal muscle : Inhibition of nitric oxide synthase inhibits walking speed in rats. In: Nitric Oxide - Biology and Chemistry. 2001 ; Vol. 5, No. 3. pp. 219-232.
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