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   <subfield code="a">Role of nitric oxide in muscle regeneration following eccentric muscle contractions in rat skeletal muscle</subfield>
   <subfield code="h">[Elektronische Daten]</subfield>
   <subfield code="c">[Tomonobu Sakurai, Osamu Kashimura, Yutaka Kano, Hideki Ohno, Li Ji, Tetsuya Izawa, Thomas Best]</subfield>
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   <subfield code="a">We examined the role of nitric oxide (NO) in muscle repair and regeneration following repetitive eccentric contractions (ECC). A standardized exercise protocol was used to create eccentric contraction-induced injury to the left tibialis anterior muscle of 48 male Wistar rats (body wt 250-350g), using a customized isokinetic test device and a bout of 40 ECCs under electrical stimulation. A nitric oxide synthase inhibitor, N(G)-nitro-l-arginine-methyl ester (l-NAME; 35mgkg−1day−1), was included in the diet for half the animals (n=24) beginning 3days prior to the ECC and continuing throughout the experiment, whereas the other half (n=24) received a control diet. ECC/+l-NAME and ECC/−l-NAME were killed after the ECC protocol at 0, 1, 3 and 7days (n=6 on each day). An unexercised contralateral limb with and without l-NAME infusion served as a respective control muscle at each time point. Muscle NO content, skeletal muscle damage, leukocyte infiltration, calpain activity, and MyoD and myogenin expression were assessed. NO has both pro-inflammatory and anti-inflammatory properties, and several possible roles for NO in skeletal muscle damage have been postulated. NO content was greater in the ECC/−l-NAME group at all time points (p&lt;0.05) compared to ECC/+l-NAME. Additionally, significant differences in NO content were observed on day0 (p&lt;0.05), and day3 (p&lt;0.05), ECC/+l-NAME versus ECC/−l-NAME. One day following the bout of ECC, and NO levels were increased in the ECC/−l-NAME group. Three days following ECC, there was greater myofiber damage (measured by β-glucuronidase activity) and leukocyte invasion in the ECC/−l-NAME group as compared to the ECC/+l-NAME group. One day after ECC, calpain activity was significantly increased in ECC/−l-NAME compared with control muscles (p&lt;0.05). On days3 and 7, Myo-D and myogenin gene expression was increased in both groups; however, the degree of regeneration was less in the ECC/+l-NAME-treated animals. These data suggest that NO dynamics have important implications in the regulation of various factors during skeletal muscle regeneration following damaging eccentric muscle contractions.</subfield>
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   <subfield code="a">The Physiological Society of Japan and Springer Japan, 2013</subfield>
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   <subfield code="a">Skeletal muscle</subfield>
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   <subfield code="a">Sakurai</subfield>
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