Effective therapy to reduce skeletal muscle injury associated with severe or eccentric exercise is needed. The purpose of this study was to determine if adenosine receptor stimulation can mediate protection from eccentric exercise-induced muscle injury. Downhill treadmill exercise (-15 º) was used to induce eccentric contraction mediated skeletal muscle injury. Experiments were conducted in both normal wild type (WT) mice and also in β-sarcoglycan knockout dystrophic mice, animals which show an exaggerated muscle damage with the stress of exercise. In the vehicle treated WT animals eccentric exercise increased serum creatine kinase (CK) greater than 3-fold to 358.9 ± 62.7 U/L (SE). This increase was totally abolished by stimulation of the A3 receptor. In the dystrophic β-sarcoglycan-null mice, eccentric exercise caused CK levels to reach 55,124 ± 5558 U/L. A3 receptor stimulation in these animals reduced the CK response by nearly 50%. In the dystrophic mice at rest 10% of the fibers were found to be damaged, as indicated by Evans blue dye staining. While this percent was doubled after exercise, A3 receptor stimulation eliminated this increase. Neither the A1 receptor agonist CCPA (0.05 mg/kg) nor the A2A receptor agonist CGS21680 (0.07 mg/kg) protected skeletal muscle from eccentric contraction injury in WT or dystrophic mice. The protective effect of adenosine A3 receptor stimulation was absent in which genes for phospholipase C β2/β3 (PLCβ2/β3) and β-sarcoglycan were deleted. The present study elucidates a new protective role of the A3 receptor and PLCβ2/β3 and points to a potentially effective therapeutic strategy for eccentric contraction-induced skeletal muscle injury.
- Copyright © 2010, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology