In vivo inhibition of nitric oxide synthase impairs upregulation of contractile protein mRNA in overloaded plantaris muscle

Jeff E. Sellman, Keith C Deruisseau, Jenna L. Betters, Vitor A. Lira, Quinlyn A. Soltow, Joshua T. Selsby, David S. Criswell

Research output: Contribution to journalArticle

48 Scopus citations


Inhibition of nitric oxide synthase (NOS) activity in vivo impedes hypertrophy in the overloaded rat plantaris. We investigated the mechanism for this effect by examining early events leading to muscle growth following 5 or 12 days of functional overload. Male Sprague-Dawley rats (∼350 g) were randomly divided into three treatment groups: control, NG-nitro-L-arginine methyl ester (L-NAME; 90 mg·kg-1·day-1), and 1-(2-trifluoromethyl-phenyl)-imidazole (TRIM; 10 mg·kg-1·day-1). Unilateral removal of synergists induced chronic overload (OL) of the right plantaris. Sham surgery performed on the left hindlimb served as a normally loaded control. L-NAME and TRIM treatments prevented OL-induced skeletal α-actin and type I (slow) myosin heavy chain mRNA expression at 5 days. Conversely, neither L-NAME nor TRIM affected hepatocyte growth factor or VEGF mRNA responses to OL at 5 days. However, OL induction of IGF-I and mechanogrowth factor mRNA was greater (P < 0.05) in the TRIM group compared with the controls. Furthermore, the phosphorylated-to-total p70 S6 kinase ratio was higher in OL muscle from NOS-inhibited groups, compared with control OL. At 12 days of OL, the cumulative proliferation of plantaris satellite cells was assessed by subcutaneous implantation of time release 5′-bromo-2′-deoxyuridine pellets during the OL-inducing surgeries. Although OL caused a fivefold increase in the number of mitotically active (5′-bromo-2′-deoxyuridine positive) sublaminar nuclei, this was unaffected by concurrent NOS inhibition. Therefore, NOS activity may provide negative feedback control of IGF-I/p70 S6 kinase signaling during muscle growth. Moreover, NOS activity may be involved in transcriptional regulation of skeletal α-actin and type I (slow) myosin heavy chain during functional overload.

Original languageEnglish (US)
Pages (from-to)258-265
Number of pages8
JournalJournal of Applied Physiology
Issue number1
StatePublished - Jan 2006
Externally publishedYes



  • 1-(2-trifluoromethyl-phenyl)-imidazole
  • Functional overload
  • Insulin-like growth factor-I
  • N-nitro-L-arginine methyl ester
  • p70 S6 kinase

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Orthopedics and Sports Medicine
  • Physical Therapy, Sports Therapy and Rehabilitation

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