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

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 and David S Criswell
Journal of applied physiology (1985), Vol.100(1), pp.258-265
01/2006
DOI: 10.1152/japplphysiol.00936.2005
PMID: 16166235

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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 (approximately 350 g) were randomly divided into three treatment groups: control, N(G)-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 alpha-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 alpha-actin and type I (slow) myosin heavy chain during functional overload.
Contractile Proteins - genetics Muscular Atrophy Nitric Oxide Synthase - antagonists & inhibitors Rats Male Muscle, Skeletal - injuries NG-Nitroarginine Methyl Ester - administration & dosage RNA, Messenger - metabolism Rats, Sprague-Dawley Enzyme Inhibitors - administration & dosage Animals Muscle, Skeletal - drug effects Muscle, Skeletal - physiopathology Ankle Joint - physiopathology Nitric Oxide Synthase - metabolism Contractile Proteins - metabolism Cumulative Trauma Disorders Insulin-Like Growth Factor I - metabolism

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