Effect of intermittent and stepwise administration of a beta-adrenergic agonist,L644,969, on rat growth performance and skeletal muscles

The effects of intermittent and stepwise administration of a β-adrenergic agonist, L644,969 on rat growth performance and skeletal muscle growth were investigated in two studies. In experiment 1, 34 juvenile male rats were randomly assigned to two treatment groups: (1) control, 0 ppm L644,969 for 21 days; (2) BL10, 10 ppm of L644,969 for 7 days, then 0 ppm L644,969 for another 7 days, plus 10 ppm of L644,969 for the final 7 days. L644,969 increased (P < 0.05) weight gain during the 7 day initial administration period. When L644,969 was withdrawn, no difference in weight gain was observed between the two groups. Re-administration of L644,969 after the withdrawal period increased (P < 0.01) weight gain up to 3 days of re-administration, but no effect was observed thereafter. In experiment 2, 18 juvenile female rats were divided into three groups: (1) control, 0 ppm L644,969 for 22 days; (2) BL10, 10 ppm L644,969 for 22 days; (3) BL10–60, 10 ppm L644,969 for 11 days, then 60 ppm L644,969 for another 11 days. Feeding 10 ppm L644,969 increased (P < 0.05) the rate of weight gain up to 11 days, but not thereafter. Raising the dose of L644,969 from 10 to 60 ppm increased body weight gain during the initial 8 day period, but no effect was observed thereafter. Weights of skeletal muscles and heart were significantly increased by 10 ppm L644,969. Raising the dose to 60 ppm increased the mean skeletal muscle weights without statistical significance. Muscular concentration of cAMP was significantly decreased by the long-term administration of L644,969. These results suggest that re-administration of the β-adrenergic agonists or increasing the dose of β-adrenergic agonists during the diminished response period could sustain the capability of the compound to enhance body weight gain.