In vivo inhibition of nitric oxide synthase impairs upregulation of contractile protein mRNA in overloaded plantaris muscle
Document Type
Article
Publication Title
Journal of Applied Physiology
Abstract
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. Copyright © 2006 the American Physiological Society.
First Page
258
Last Page
265
DOI
10.1152/japplphysiol.00936.2005
Publication Date
1-1-2006
Recommended Citation
Sellman, Jeff E.; DeRuisseau, Keith C.; Betters, Jenna L.; Lira, Vitor A.; Soltow, Quinlyn A.; Selsby, Joshua T.; and Criswell, David S., "In vivo inhibition of nitric oxide synthase impairs upregulation of contractile protein mRNA in overloaded plantaris muscle" (2006). Basic Sciences Faculty Publications. 59.
https://doi.org/10.1152/japplphysiol.00936.2005
https://collections.uhsp.edu/basic-sciences_pubs/59