Effect of the beta(2)-agonist clenbuterol on the locomotor activity of rat submitted to a 14-day period of hypodynamia-hypokinesia.

The beta(2)-adrenergic agonist clenbuterol is known for its anabolic action on normal and atrophied muscles. The aim of this work was to evaluate if chronic clenbuterol administration could prevent alterations in the locomotor activity induced by hindlimb suspension. The effects of clenbuterol were evaluated in three studies: muscle morphological characteristics, observation of locomotor movement and electromyographic activity of soleus and gastrocnemius muscles. Rats were divided into four groups: control (CON, morphological study only), hindlimb suspended (HS), clenbuterol administered (CB, 2 mg kg(-1) per day in drinking water), and hindlimb suspended+clenbuterol administered (HSCB). The soleus muscle weight was reduced in the two suspended groups (HS and HSCB) but did not change after clenbuterol treatment. By contrast, the gastrocnemius weight was not affected by suspension but was increased by clenbuterol (CB and HSCB). Some locomotor deficits were always observed in HS rats (unstable gait, ankle hyperextension, ellipsis). Clenbuterol administration did not prevent these perturbations. Cycle duration and soleus burst duration were increased in the three groups. Soleus mean EMG (burst area/duration) was decreased in HS rats, but not in the two other groups. For the gastrocnemius, burst duration was increased in CB rats, decreased in HSCB rats and unchanged in HS ones; mean EMG did not change. In conclusion, clenbuterol cannot be used as a countermeasure to reduce the alteration in locomotor performance. Moreover, our results suggest that this alteration is specifically related to changes in neuronal properties.

Effects of beta(2)-agonist clenbuterol on biochemical and contractile properties of unloaded soleus fibers of rat.

The effects of clenbuterol beta(2)-agonist administration were investigated in normal and atrophied [15-day hindlimb-unloaded (HU)] rat soleus muscles. We showed that clenbuterol had a specific effect on muscle tissue, since it reduces soleus atrophy induced by HU. The study of Ca(2+) activation properties of single skinned fibers revealed that clenbuterol partly prevented the decrease in maximal tension after HU, with a preferential effect on fast-twitch fibers. Clenbuterol improved the Ca(2+) sensitivity in slow- and fast-twitch fibers by shifting the tension-pCa relationship toward lower Ca(2+) concentrations, but this effect was more marked after HU than in normal conditions. Whole muscle electrophoresis indicated slow-to-fast transitions of the myosin heavy chain isoforms for unloaded and for clenbuterol-treated soleus. The coupling of the two latter conditions did not, however, increase these phenotypical transformations. Our findings indicated that clenbuterol had an anabolic action and a beta(2)-adrenergic effect on muscle fibers and appeared to counteract some effects of unloading disuse conditions.