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 250-350 g), 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; 35 mg kg-1 day-1), was included in the diet for half the animals (n = 24) beginning 3 days 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 7 days (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 < 0.05) compared to ECC/+l-NAME. Additionally, significant differences in NO content were observed on day 0 (p < 0.05), and day 3 (p < 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 < 0.05). On days 3 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. © 2013 The Physiological Society of Japan and Springer Japan.
CITATION STYLE
Sakurai, T., Kashimura, O., Kano, Y., Ohno, H., Ji, L. L., Izawa, T., & Best, T. M. (2013). Role of nitric oxide in muscle regeneration following eccentric muscle contractions in rat skeletal muscle. Journal of Physiological Sciences, 63(4), 263–270. https://doi.org/10.1007/s12576-013-0262-y
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