Clenbuterol attenuates muscle atrophy and dysfunction in hindlimb-suspended rats

Background: Muscle wasting and dysfunction is a significant problem in prolonged exposure to microgravity. Hypothesis: This study tested the hypothesis that a β-adrenergic agonist (clenbuterol) could attenuate the effects of 14 d of unweighting on mixed fiber type skeletal muscle. Methods: Female, Sprague-Dawley rats were maintained in cages as: 1. controls (C; n = 12); 2. hindlimb suspended via tail casting (HLU; n = 12); 3. clenbuterol injected daily (3 mg · kg ) (CL; n = 10); or 4. hindlimb suspended and injected with clenbuterol daily (3 mg · kg-1) (HLU + CL; n = 12). Results: At the end of the study, both CL and HLU + CL had higher body weights compared with HLU (p < 0.05). Gastrocnemius mass (wet weight and muscle weight/body weight) and maximal tetanic force were significantly decreased during HLU (p < 0.05) (mean ± SE; mass: C = 1.6 ± 0.04 g, HLU = 1.2 ± 0.05 g; force: C = 3483 ± 113 g, HLU = 2765 ± 52 g). Clenbuterol attenuated the decrease in both mass and force generation (mass: HLU + CL = 1.4 ± 0.04 g; force: HLU + CL = 3162 ± 135), Twitch tension during HLU (1057 ± 72 g) was significantly less (p < 0.05) than during C (1362 ± 61 g), and clenbuterol did not attenuate this loss. HLU caused a decrease (p < 0.05) in force at 30 Hz and decreased one-half relaxation time (1/2 RT) (p < 0.05) from 30 ± 2 to 25 ± 2 ms. Clenbuterol caused further decreases (p < 0.05) in both force (20 and 30 Hz) and 1/2 RT. Conclusions: These data suggest that a β-adrenergic agonist may be of benefit in attenuating wasting and the reduced maximal force seen during periods of unweighting in mixed fiber type muscle. -1