Basal, but not overload-induced, myonuclear addition is attenuated by N^G-nitro-l-arginine methyl ester (l-NAME) administration

Abstract

The purpose of this study was to examine the effect of blocking nitric oxide synthase (NOS) activity via NG-nitro-L-arginine methyl ester (L-NAME) on myonuclear addition in skeletal muscle under basal and overloaded conditions. Female Sprague-Dawley rats (approx. 220 g) were placed into 1 of the following 4 groups (n = 7-9/group): 7-day skeletal muscle overload (O), sham operation (S), skeletal muscle overload with L-NAME treatment (OLN), and sham operation with L-NAME treatment (SLN). Plantaris muscles were overloaded via bilateral surgical ablation of the gastrocnemius muscles and L-NAME (0.75 mg/mL) was administered in the animals' daily drinking water starting 2 days prior to surgery and continued until sacrifice. Myonuclear addition was assessed as subsarcolemmal incorporation of nuclei labeled with 5-bromo-2'-deoxyuridine (approx. 25 mg.(kg body mass)-1.day-1) delivered via osmotic pump during the overload period. As expected, muscle wet mass, total protein content, fiber cross-sectional area, and myonuclear addition were significantly higher (p <or= 0.05) in O vs. S; however, only the increase in wet mass and total protein content (per body mass) were attenuated by L-NAME administration. Interestingly, L-NAME significantly reduced myonuclear addition by 75% in non overloaded muscles (SLN vs. S). Muscle hepatocyte growth factor protein content increased with overload, but was unaffected by L-NAME in either loading state. These data indicate that NOS inhibition in rat plantaris muscle attenuates myonuclear addition under basal, but not overloaded, conditions.

Skeletal Muscle Activity and the Fate of Myonuclei

“…HGF binds the c–Met–receptor of the myosatellite cells, leading to their activation. On the other hand, data exist indicating that, during compensatory hypertrophy caused by the synergistic–muscle removal, myonuclei activation can occur independently from the NOS inhibitor [79]. In the model of Wozniak et al .…”