Effects of [beta]2-agonist administration and exercise on
contractile activation of skeletal muscle fibers.
Lynch, Gordon S., Alan Hayes, Siun P. Campbell & David A. Williams.
Muscle and Cell Physiology Laboratory, Department of Physiology,
The University of Melbourne, Parkville, Victoria, 3052, Australia
APStracts 3:0244A, 1996.
Clenbuterol, a [beta]2-adrenoceptor agonist, has been suggested to
have therapeutic potential for the treatment of muscle wasting
diseases, yet its effects, especially at the single fiber level have
not been fully characterized. Male C57BL/10 mice were allocated into
three groups. One group of mice (CONTROL-TREATED) were administered
clenbuterol (2 mg/kg/day) via their drinking water for 15 weeks. In
addition to receiving clenbuterol, another group of mice (TRAINED
-TREATED) underwent daily (5 days/week), low-intensity (unweighted
swimming) training, 1 hour/day, to determine whether exercise
modified clenbuterol's effects. Another group (CONTROL) remained in
their cages and were not administered clenbuterol. Ca2+- and Sr2+
-activated isometric contractile characteristics were determined for
skinned extensor digitorum longus (EDL) and soleus muscle fibers from
all groups. Fast-twitch fibers from the EDL and soleus muscles of
TREATED mice exhibited a decrease in their sensitivity to Ca2+.
Endurance exercise offset clenbuterol's effects, demonstrated by the
similar values for Ca2+-sensitivity exhibited by the fibers from the
TRAINED-TREATED group and those of the sedentary, untreated CONTROL
animals. Clenbuterol did not affect the normalized maximum tension
(Po) of either fast- or slow-twitch single muscle fibers. Long-term
clenbuterol treatment increased the proportion of fast-twitch fibers
in the soleus. Endurance training increased the proportion of fibers
with high SDH activity in the EDL muscle of the TRAINED-TREATED group
compared with the CONTROL-TREATED animals, and increased the
proportion of fibers with intermediate levels of SDH activity in the
soleus. If clenbuterol is to be used as a therapeutic agent in the
treatment of muscle wasting disorders (e.g. dystrophy) it might also
be suggested that, if possible, some form of low-intensity exercise
be encouraged such that the existing skeletal muscle mass be
maintained whilst the potentially deleterious slow to fast fiber type
transformations are minimised. In the mouse, the performance of even
low-intensity exercise (e.g. unweighted swimming) appears to prevent
these effects.
Received 23 January 1995; accepted in final form 3 May 1996.
APS Manuscript Number A81-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 May 96