Clenbuterol accelerates recovery after immobilization-induced atrophy of rat hindlimb muscle.

Using immunohistochemistry, we investigated whether daily administration of clenbuterol (CLE; 1 mg/kg body weight per day) accelerates recovery after casted immobilization(IMM)-induced atrophy of fast-twitch plantaris and slow-twitch soleus muscles. Adult male Sprague-Dawley rats were assigned to the control (CON), casted immobilization (IMM), casted immobilization following recovery control (RCON), and casted immobilization following recovery with CLE administration (RCLE) groups. Casted immobilization and recovery periods were 9 and 14days, respectively. Rats of the CON group were subjected to the experiment simultaneously with the IMM group. Nine days of immobilization induced muscle fiber atrophy, which was greater in the soleus muscle than in the plantaris muscle. After the 2-week recovery period, the cross-sectional areas of each fiber type in both muscles were higher in the RCON group than in the IMM group. The cross-sectional areas of each fiber type in both muscles in the RCLE group were larger than those in the RCON group. The myonuclear number of each fiber type of the plantaris muscle in the RCON and RCLE groups was higher than that in the CON group. In contrast, the myonuclear number per fiber of the soleus muscle was not affected by hindlimb immobilization, reloading, and clenbuterol administration regardless of muscle fiber type. These results suggest that CLE accelerates the recovery of atrophied plantaris and soleus muscles fibers and that their mechanisms of responses to CLE in both muscles may be different during recovery period after muscle atrophy.

Casted-immobilization downregulates glucocorticoid receptor expression in rat slow-twitch soleus muscle.

AIMS: Glucocorticoids bind to the glucocorticoid receptor (GR) and increase catabolism of muscle proteins via the ubiquitin-proteasome pathway. Activation of ß(2)-adrenergic receptor (ß(2)-AR) in skeletal muscle has been shown to induce muscle hypertrophy by promoting muscle protein synthesis and/or attenuating protein degradation. The aim of this study was to investigate the correlation between disuse-induced muscle atrophy, and expression of GR and ß(2)-AR. METHODS: Rats were subjected to casted-immobilization (knee and foot arthrodesis), a model for muscle disuse, for 10 days. Fast-twitch (extensor digitorum longus: EDL) and slow-twitch (soleus: SOL) muscles were isolated and subsequently used for analysis. The expression of GR and ß(2)-AR was analyzed by real-time RT-PCR and western blotting. In addition, we analyzed plasma catecholamine and corticosterone concentrations by ELISA. KEY FINDINGS: Casted-immobilization-induced muscle atrophy was much greater in the SOL muscle than in the EDL muscle. Casted-immobilization decreased the expression of GR mRNA and protein in the SOL muscle but not in the EDL muscle. Although the expression of ß(2)-AR protein in the cytosol and membrane-rich fractions was not changed by casted-immobilization in either muscle, casted-immobilization decreased the expression of ß(2)-AR mRNA in the SOL muscle. Plasma catecholamine and corticosterone concentrations, however, were largely unaffected by casted-immobilization during the experimental period. SIGNIFICANCE: This study provides evidence that casted-immobilization-induced muscle disuse downregulates GR expression in slow-twitch muscle. These results suggest that muscle disuse suppresses glucocorticoid signals, such as muscle protein breakdown and transcription of the ß(2)-AR gene, via downregulation of GR expression in slow-twitch muscle.

Branched-chain amino acid supplementation increases the lactate threshold during an incremental exercise test in trained individuals.

The effects of branched-chain amino acid (BCAA) supplementation on the lactate threshold (LT) were investigated as an index of endurance exercise capacity. Eight trained male subjects (21+/-2 y) participated in a double-blind crossover placebo-controlled study. The subjects were randomly assigned to two groups and were provided either a BCAA drink (0.4% BCAA, 4% carbohydrate; 1,500 mL/d) or an iso-caloric placebo drink for 6 d. On the 7th day, the subjects performed an incremental loading exercise test with a cycle ergometer until exhaustion in order to measure the LT. The test drink (500 mL) was ingested 15-min before the test. Oxygen consumption VO2 and the respiratory exchange ratio (RER) during the exercise test were measured with the breath-by-breath method. Blood samples were taken before and during the exercise test to measure the blood lactate and plasma BCAA concentrations. The same exercise test was performed again 1 wk later. BCAA supplementation increased the plasma BCAA concentration during the exercise test, while plasma BCAA concentration decreased in the placebo trial. The RER during the exercise test in the BCAA trial was lower than that in the placebo trial (p<0.05). The VO2 and workload levels at LT point in the BCAA trial were higher than those in the placebo trial (VO2: 29.8+/-6.8 vs. 26.4+/-5.4 mL/kg/min; workload: 175+/-42 vs. 165+/-38 W, p<0.05, respectively). The VO2max in the BCAA trial was higher than that in the placebo trial (47.1+/-5.7 vs. 45.2+/-5.0 mL/kg/min, p<0.05). These results suggest that BCAA supplementation may be effective to increase the endurance exercise capacity.

Age-related differences in the effect of running training on cardiac Myosin isozyme composition in rats.

We examined the effect of running training on age-related changes in cardiac myosin isozyme composition in rats. Female Fischer 344 rats (6, 12, 20, and 27 months old) were divided into two groups: sedentary control and trained. The trained group rats were trained by treadmill running for up to 60 minutes per day, 5 days per week for 8 weeks at up to 30 m per minute. In sedentary control rats, the proportion of V1 myosin, that is, alpha-myosin heavy chain (MyHC) isoform, decreased progressively from 6 to 27 months of age. In the younger age groups (6 or 12 months old), there was a shift from V1 myosin to V3 myosin (beta-MyHC isoform) in trained hearts. However, the training program did not induce a cardiac myosin isozyme transition in older rats (20 or 27 months old). These results suggest that the mechanisms mediating the responses of cardiac muscle to running training alter during aging.