Role of nitric oxide in muscle regeneration following eccentric muscle contractions in rat skeletal muscle

Abstract

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.

Effects of Beetroot Juice on Recovery of Muscle Function and Performance between Bouts of Repeated Sprint Exercise

“…It was beyond the scope of this study to examine the role of other mechanisms by which BTJ could attenuate muscle damage, but owing to the seemingly pleotropic nature of phenolic and betalainic compounds and NO, there are a number of possible candidates. For instance, other effects associated with phenolic compounds and NO donors akin to BTJ are anti-inflammatory [25,33] and regenerative, in so far as they appear to have a regulatory role in phagocytosis and promote satellite cell proliferation in skeletal muscle [53,54,55]. Increasing in vivo NO availability has also demonstrated additional biochemical effects that, conceivably, could contribute to improved functional recovery after exercise, such as reduced calpain activity [56], increased muscle blood flow [57,58], and enhanced muscle power potential, possibly via improved Ca 2+ handing [59,60].…”

Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training?

“…), while treatment with the NOS inhibitor l ‐NAME may delay muscle regeneration following acute eccentric exercise (Sakurai et al . ).…”

The Efficacy of Microcurrent Therapy on Eccentric Contraction-Induced Muscle Damage in Rat Fast-Twitch Skeletal Muscle

“…Our previous study, using the same model for ECC as in this study [22], has demonstrated that up to 4 days after ECC, ECC-related reductions in myosin ATPase activity are not accompanied by proteolysis of myosin heavy chain where myosin ATPase is situated. It has been shown that the concentration of nitric oxide increases in the muscle cell for several days after ECC [31] and that increased nitric oxide adversely affects the contractile proper- Muscle damage and resultant depressions in muscle performance are universal symptoms familiar to most athletes, because muscle contractions during many of sport activities and training include a substantial eccentric component.…”