Effects of Nitric Oxide Synthase Inhibition on Fiber-Type Composition, Mitochondrial Biogenesis, and SIRT1 Expression in Rat Skeletal Muscle.
It was hypothesized that nitric oxide synthases (NOS) regulated SIRT1 expression and lead to a corresponding changes of contractile and metabolic properties in skeletal muscle. The purpose of the present study was to investigate the influence of long-term inhibition of nitric oxide synthases (NOS) on the fiber-type composition, metabolic regulators such as and silent information regulator of transcription 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), and components of mitochondrial biogenesis in the soleus and plantaris muscles of rats. Rats were assigned to two groups: control and NOS inhibitor (N (ω)-nitro-L-arginine methyl ester hydrochloride (L-NAME), ingested for 8 weeks in drinking water)-treated groups. The percentage of Type I fibers in the L-NAME group was significantly lower than that in the control group, and the percentage of Type IIA fibers was concomitantly higher in soleus muscle. In plantaris muscle, muscle fiber composition was not altered by L-NAME treatment. L-NAME treatment decreased the cytochrome C protein expression and activity of mitochondrial oxidative enzymes in the plantaris muscle but not in soleus muscle. NOS inhibition reduced the SIRT1 protein expression level in both the soleus and plantaris muscles, whereas it did not affect the PGC-1α protein expression. L-NAME treatment also reduced the glucose transporter 4 protein expression in both muscles. These results suggest that NOS plays a role in maintaining SIRT1 protein expression, muscle fiber composition and components of mitochondrial biogenesis in skeletal muscle. Key pointsNOS inhibition by L-NAME treatment decreased the SIRT1 protein expression in skeletal muscle.NOS inhibition induced the Type I to Type IIA fiber type transformation in soleus muscle.NOS inhibition reduced the components of mitochondrial biogenesis and glucose metabolism in skeletal muscle.
Faculty of Life Design, Tohoku Institute of Technology , Taihaku-ku, Sendai, Japan.
Masataka
M
Suwa
Faculty of Education, Nakamura Gakuen University , Jonan-ku, Fukuoka, Japan.
Hiroshi
H
Nakano
Institute of Sport Science, Faculty of Physical Education and Sport Science, Semmelweis University, Budapest , Hungary.
Zsolt
Z
Radak
Faculty of Arts and Science, Kyushu University , Kasuga, Fukuoka, Japan ; Graduate School of Human-Environment Studies, Kyushu University , Kasuga, Fukuoka, Japan.
Shuzo
S
Kumagai
Mitochondrial biogenesis; muscle fiber composition; nitric oxide; nitric oxide synthase; silent information regulator of transcription 1