Clenbuterol attenuates muscle atrophy and dysfunction in hindlimb-suspended rats

Abstract

Background: Muscle wasting and dysfunction is a significant problem in prolonged exposure to microgravity.

Hypothesis: This study tested the hypothesis that a beta-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 x kg(-1)) (CL; n = 10); or 4. hindlimb suspended and injected with clenbuterol daily (3 mg x 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 beta-adrenergic agonist may be of benefit in attenuating wasting and the reduced maximal force seen during periods of unweighting in mixed fiber type muscle.