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-blockade increases skeletal muscle
-adrenergicreceptor density and enhances contractile force
1 Département d'Éducation Physique, 2 Département de Biochimie, and 3 Groupe de Recherche sur le Système Nerveux Autonome, Université de Montréal, Montreal, Quebec, Canada H3C 3J7
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
Murphy, René J. L., Phillip F. Gardiner, Guy Rousseau,
Michel Bouvier, and Louise Béliveau. Chronic 
-blockade
increases skeletal muscle -adrenergic-receptor density and enhances
contractile force. J. Appl. Physiol.
83(2): 459-465, 1997.
The effects of a chronic 14-day
administration of a selective
2-adrenergic-receptor antagonist (ICI-118551) on skeletal muscle were evaluated in female Sprague-Dawley rats. Chronic ICI-118551 treatment did not modify muscle
mass, oxidative potential, or protein concentration of the medial
gastrocnemius muscle, suggesting that maintenance of these skeletal
muscle characteristics is not dependent on
2-adrenergic-receptor stimulation. However, the drug treatment increased
-adrenergic-receptor density of the lateral gastrocnemius (42%) and
caused an increase in specific (g/g) isometric in situ contractile
forces of the medial gastrocnemius [twitch, 56%; tetanic (200 Hz), 28%]. The elevated contractile forces observed after a
chronic treatment with ICI-118551 were completely abolished when the
2-adrenergic antagonist was
also administered acutely before measurement of contractile forces,
suggesting that this response is
2-adrenergic-receptor dependent. Possible mechanisms for the increased forces were studied. Caffeine administration potentiated twitch forces but had little effect
on tetanic force in control animals. Administration of dibutyryl
adenosine 3
,5-cyclic monophosphate in control animals also resulted in small increases of twitch force but did not modify tetanic forces. We conclude that increases in -adrenergic-receptor density and the stimulation of the receptors by endogenous
catecholamines appear to be responsible for increased contractile
forces but that the mechanism remains to be demonstrated.
contractile properties; ICI-118551
INTRODUCTION DIFFERENT SKELETAL MUSCLE fiber types have been shown
to express different densities and types of Other observations suggest that The purpose of this study was to determine the effects of chronic
blockade of METHODS
-adrenergic receptors
(14). For instance, higher densities of -adrenergic receptors are
present in slow skeletal muscles (10), and atypical -adrenergic
receptors are probably the most important type, representing up to 80%
of -adrenergic receptors of the soleus muscle (20, 23). However, 2-adrenergic receptors are
believed to be the main type of adrenergic receptors in fast skeletal
muscle (10). Recent work has focused on characterizing skeletal muscle
-adrenergic receptors, but their functional roles have not been
completely elucidated. These receptors could be involved in several
aspects of muscle function, including stimulation of glycogenolysis
(28), triglyceride lipolysis (27), muscle oxygen consumption (26), ion
exchange (19), and increasing muscle force generation (28). These
effects could differ in various muscles because of the number
and/or type of -adrenergic receptors present. For instance,
2-adrenergic-agonist stimulation of Na+ extrusion and
K+ uptake has been reported to be
much greater in slow than in fast skeletal muscles (19). Conversely,
the inotropic effects of -agonists are observed solely in fast
skeletal muscles (28), but the mechanism underlying this effect is not
well understood. -Adrenergic-receptor stimulation causes a cascade
of events leading to the intracellular accumulation of the second
messenger adenosine 3,5-cyclic monophosphate (cAMP).
However, the intracellular site of cAMP action in the potentiation of
fast skeletal muscle force is unknown.
-adrenergic receptors may be
involved in skeletal muscle adaptations to changes in activity level.
For example, skeletal muscle -adrenergic-receptor density has been
shown to be correlated with both the oxidative potential (29) and the
percentage of type I fibers in skeletal muscle (14). Furthermore,
chronic 2-adrenergic-receptor
stimulation causes increased skeletal muscle mass in several animal
species (10, 30). Finally, the widely used clinically nonspecific -adrenergic blockers are usually associated with reduced exercise capacity (25). In previous attempts to determine the roles of skeletal
muscle 2-adrenergic receptors,
nonspecific -adrenergic blockers or a combination of nonspecific and
1-selective blockers have been
used (9). However, the effects of chronic selective 2-adrenergic-receptor blockade
on skeletal muscle properties have not been studied in detail.
2-adrenergic
receptors on skeletal muscle properties. Muscle isometric contractile
properties, mass, protein concentration, fiber types, cytochrome
oxidase activity, as well as -adrenergic-receptor density were
measured in selected muscles after chronic treatment with a selective
2-adrenergic-receptor
antagonist.
2-adrenergic antagonist, at a
dose of 5 mg/kg by subcutaneous injections twice daily. Rats of the
control group received two daily subcutaneous injections of the vehicle
composed of 20 parts saline (0.09%), 1 part hydrochloric acid (11 M),
and 4 parts methanol. All treatments were administered for
14 days. At that time, ICI-treated rats were either subjected to a
washout period of 18-20 h or given another ICI injection to block
the receptors acutely ~2 h before measurement of contractile
properties.
Muscle mass and contractile properties.
The responses of several hindlimb skeletal muscles to
2-adrenergic-receptor blockade
were studied. For contractile properties, the gastrocnemius muscle was
preferentially studied because it is a readily accessible fast skeletal
muscle and it responds well to selective
2-adrenergic-receptor agonists
(5, 17). After the drug treatment, each rat was anesthetized with an
intraperitoneal injection of pentobarbital sodium (45 mg/kg) and was
surgically prepared for the measurement of in situ isometric
contractile properties of the medial gastrocnemius. Briefly, the left
hindlimb was shaved, and an incision through the skin was made on the
caudal surface. The ankle extensor muscles were exposed surgically, and all muscles except the medial gastrocnemius were denervated. The vasculature was left undisturbed. The calcaneous was cut, and a small
piece of bone was left attached to the Achilles tendon. The insertion
of the soleus, plantaris, and gastrocnemius muscles was attached to a
force transducer by using silk ligature. The animal's body and left
hindlimb were stabilized by using a brace for the spine, a drill bit
inserted perpendicularly into the femur, as well as a clamp on the left
foot. To maintain the muscle temperature at ~36°C, the hindlimb
skin was used to form a recirculating oil bath. The animal rested on a
heating pad, and body temperature was monitored and adjusted as needed.
The intact sciatic nerve was stimulated (model S88 stimulator, Grass)
with a bipolar silver electrode, and forces were recorded on
microcomputer or FM tape. A 0.05-ms square-wave pulse was used
throughout the experiment. The voltage necessary to obtain a maximal
twitch response was determined, and supramaximal voltage was
subsequently delivered to the sciatic nerve. A short (200-ms) tetanic
(200-Hz) contraction was delivered, and then the muscle was set at
optimal length for a maximal twitch response. Forces were measured in
response to a single twitch and at 25-, 50-, 100-, 200-, 300-, and
400-Hz stimulation frequencies before measurement of a fatigue index. The fatigue protocol consisted of a 5-min stimulation period at 75 Hz,
100 ms, three times per second (17). After the measurement of
contractile properties, the soleus, plantaris, medial, and lateral
gastrocnemius muscles of both hindlimbs were removed, blotted dry,
weighed, and frozen in liquid nitrogen. The muscle samples were stored
at 
80°C until analysis.
Acute ICI experiments and caffeine experiments.
In these experiments, previously untreated control animals
were prepared for the measurement of contractile properties as described in Muscle mass and contractile
properties. Control twitch and tetanic
forces were measured and the animals were injected intraperitoneally
with ICI at a dose of 5 mg/kg or with the vehicle. Twitch forces were
then monitored and recorded at different time intervals. Tetanic
(200-Hz) tension was also recorded.
In the caffeine experiments, animals also had a catheter inserted in
the jugular vein. Twitch and tetanic contractile forces were recorded,
and then a 75 mg/kg dose of caffeine (12) was infused via the catheter
while twitch contractions were monitored. When twitch forces were
maximal, a 600-ms, 200-Hz tetanic contraction was delivered and force
was recorded. In control animals, the contractile forces were recorded
at approximately the same time after administration of a corresponding
volume of the saline vehicle.
Dibutyryl cAMP experiments and direct vs. indirect muscle
stimulation experiments.
In these experiments, previously untreated control animals were
prepared for the measurement of contractile properties as described in
Muscle mass and contractile
properties. However, in these animals, the
soleus, plantaris, and lateral gastrocnemius muscles were carefully
dissected from the distal tendon, and the medial gastrocnemius was
isolated.
A small bath made of parafilm was constructed, and the medial
gastrocnemius muscle was incubated in the vehicle or in 3 mM dibutyryl
cAMP for 60 min. Contractile properties were measured after the
incubation period.
Indirect twitch and tetanic contractions were compared with twitch and
tetanic contractions obtained by direct stimulation of the medial
gastrocnemius muscle. Direct stimulation was delivered via two small
silver electrodes placed in the medial gastrocnemius by using
supramaximal voltage.
Muscle protein concentration.
Total and myofibrillar muscle protein concentrations were measured in
the medial gastrocnemius muscle. Each muscle was homogenized (tissue
homogenizer) individually in a potassium phosphate buffer (0.05 M, pH
7.4; 1 ml for 100 mg tissue). Aliquots of the samples were then
processed in triplicate by using the Bradford protein assay to
determine total protein concentration spectrophotometrically. Extraction of myofibrillar proteins was performed on the homogenate. Myofibrillar proteins were solubilized by two successive incubations with agitation, in ice-cold 0.3 M NaOH. Samples were mixed 2 h at
4°C before a 20-min centrifugation at 1,400 g at 4°C. Myofibrillar protein
samples were assayed in triplicate. For all assays, bovine serum
albumin was used as standard.
Cytochrome oxidase activity.
As an index of oxidative capacity, the rate of oxidation of reduced
cytochrome c by cytochrome oxidase was
measured spectrophotometrically in the soleus, plantaris, and medial
gastrocnemius muscles. Each muscle was homogenized
separately and processed in duplicate according to the methods of Smith
(24).
-Adrenergic-receptor density.
-Adrenergic-receptor density was measured in the lateral
gastrocnemius muscles because medial gastrocnemius muscles had been used for protein concentration and cytochrome oxidase activity determination. In preliminary experiments, we determined that the
-adrenergic-receptor densities of the medial gastrocnemius and
lateral gastrocnemius are similar (60 ± 8 vs. 66 ± 9 fmol/mg protein). Skeletal muscle membranes were prepared by mincing the frozen
muscles with scissors and, while the muscles were on ice, homogenizing
them with three 6- to 7-s bursts of a Polytron homogenizer set at high
speed in the following homogenization buffer: 5 mM tris(hydroxymethyl)aminomethane (Tris) and 2 mM EDTA solution (pH
7.4) containing 5 mg/l trypsine inhibitor, 5 mg/l leupeptin, and 10 mg/l benzamidine. The homogenates were centrifuged 5 min at 1,000 g at 4°C and filtered
through four layers of gauze. The supernatant was then centrifuged at
4°C (Sorvall Dupont RC26plus) for 20 min at 40,000 g. The pellets were washed by
resuspension in the homogenization medium and centrifuged a second time
at 40,000 g. The final pellets were resuspended in a 75 mM
Tris, 12.5 mM MgCl2, and 2 mM EDTA
buffer at 4°C and used immediately for all subsequent analysis.
Muscle membrane preparation protein content was determined by using the
Bradford protein assay with standards prepared using bovine serum
albumin. All samples were measured in triplicate.
To measure skeletal muscle -adrenergic-receptor density, the
following methods were used. In preliminary studies, saturation binding
experiments were performed. Thereafter, the muscle membrane preparation
was added to a saturating
[125I]iodocyanopindolol
concentration (~250 pM) without and with 10 µM alprenolol to
determine total and nonspecific binding. Sample tubes were vortexed and
incubated 90 min at room temperature. After the incubation period, the
tubes were rinsed four times with ice-cold Tris buffer (25 mM), and the
contents were filtered to separate bound and free radioligand. Vacuum
filtration of the samples was performed by using a Brandel cell
harvester and glass microfiber filters (Whatman International)
previously treated with 25 mM Tris; 0.3% polyethylenimine, and 0.1 g/100 ml bovine serum albumin. The radioactivity was
counted in a gamma counter (LKB 1271). Specific binding was calculated
as the difference between total and nonspecific binding measured in the
presence of alprenolol. In this study, the specific binding represented 69.5 ± 8.7% (means ± SD for all samples) of the total binding. All binding assays were performed in triplicate.
-Adrenergic-receptor densities are expressed in femtomoles per
milligram protein.
Immunohistochemistry.
Plantaris muscle fiber types were analyzed by using antibodies raised
against myosin heavy chain, using the methods described by Gorza (8).
Materials.
The myosin heavy chain antibodies were a gift from Dr. S. Schiaffino
(University of Padua). ICI-118551 was a gift from Cambridge Research
Biochemicals. All other chemicals are commercially available.
Statistical analysis.
All data are reported as group means ± SD. The
statistical analysis performed was a one-way analysis of variance
followed by a Tukey post hoc test when necessary. Statistical
significance was accepted at P < 0.05.
RESULTS
Absolute (kg) and relative (g/g) isometric contractile forces of the
medial gastrocnemius muscle were significantly increased in the
ICI-treated group. As illustrated in Fig.
1, twitch force was increased 56% while
tetanic force at 200 Hz was increased 28% compared with the control
group. However, the increased forces were completely abolished in
animals treated for 14 days with ICI and treated acutely with the
2-adrenergic blocker ~2 h
before the measurement of contractile properties (Fig. 1). Indeed, the contractile forces measured in these rats were slightly lower than but
not statistically different from controls.
Twitch contractile and half relaxation times were not modified
significantly by chronic or chronic and acute ICI treatment (Table
1). The fatigue index
calculated from the force decline in response to rhythmic semifused
contractions did not change after chronic
2-adrenergic-receptor blockade.
The control group maintained 26.1 ± 4.7% of the maximal force
while the ICI-treated group maintained 27.3 ± 9.1% of the maximal
force during the fatigue protocol. Examples of twitch and tetanic
(200-Hz) contractions are presented in Fig.
2.
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Direct and indirect stimulation of the medial gastrocnemius muscle of control animals resulted in similar peak twitch and tetanic forces. The difference in peak tetanic forces between direct and indirect stimulation was not statistically significant (2.8%).
Final body mass was unchanged after the drug treatment (Table
2), and daily food intake was not affected
by chronic
2-adrenergic-receptor blockade
(data not shown). Soleus, plantaris, and gastrocnemius muscle masses
were also similar in control and ICI-treated groups, as were the medial
gastrocnemius muscle total and myofibrillar protein concentrations
(Table 2). The immunohistochemically identified fiber type percentages
were not different in control and ICI-treated animals (9.2 vs. 8.9%
type I, 30.1 vs. 28.3% type IIa, and 20.2 vs. 17.0% type IIb; no. of
fibers analyzed = 1,885 control and 1,769 ICI). The oxidative
potentials of three hindlimb muscles assessed by the activity of the
enzyme complex cytochrome oxidase were also unaffected by chronic
2-adrenergic blockade (Table 2).
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However, as illustrated in Fig. 3, chronic
2-adrenergic-receptor blockade
increased the -adrenergic-receptor density by 42% in the
ICI-treated group.
-Adrenergic-receptor density (Bmax) of lateral gastrocnemius muscle
in Con and ICI. Values are means ± SD. * ICI significantly greater than Con, P < 0.05.
The increased forces observed in animals chronically treated with ICI
were not due to the drug or to a metabolite of the drug as acute
administration of ICI to control animals appeared to slightly reduce
contractile forces (Table 3). To verify
whether the increased contractile forces were due to activation of the 2-adrenergic receptors and
accumulation of the second-messenger cAMP, contractile forces were
measured in a preparation in which muscle cAMP concentrations were
elevated. This pharmacological treatment caused a small increase in
twitch force and duration but no change in tetanic force (Table 3).
Increases in sarcoplasmic reticulum calcium release could also be a
mechanism responsible for the increased forces. To verify that
possibility, caffeine was infused in control animals, and in these
experiments, twitch forces were potentiated by an average of 29.2%,
whereas tetanic force did not change significantly (Table 3).
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DISCUSSION
2-Adrenergic receptors could be
involved in maintenance or adaptation of skeletal muscle tissue
characteristics. For instance, they have been suggested to participate
in the physiological control of tissue mass by endogenous
catecholamines (22), and there is some evidence that muscle enzymatic
adaptation is regulated, at least in part, by stimulation of
2-adrenergic receptors (9). Furthermore, skeletal muscle mass, protein content, and fiber size are
increased after treatment with some
2-agonists (10, 17, 30, 31). If
the muscle's 2-adrenergic
receptors are necessary for maintenance of these characteristics,
chronic 2-adrenergic-receptor blockade could be expected to have opposite effects.
There were no changes in skeletal muscle mass after chronic
administration of ICI in this study (Table 2), which is similar to
another published report (21). However, these results contradict those
of Sillence et al. (22) and Benbachir-Lamrini et al. (1), who reported
decreases of hindlimb muscle mass and increases of soleus muscle mass
after chronic treatments with ICI, respectively. Interestingly,
Benbachir-Lamrini and collaborators observed a decrease in muscle
cross-sectional area in 4-wk-old Wistar-Kyoto normotensive rats,
whereas an increase in cross-sectional area was observed in the 8- to
10-wk-old animals. The reasons for the differences
observed in these studies could be the duration of the treatment, the
drug dose, the age, the gender, or the strain of the animals used. In
another study, we studied 16 older male Sprague-Dawley rats under the
same conditions and also found that the chronic treatment with ICI used
in this study did not change skeletal muscle mass (unpublished
observations). Decreases in skeletal muscle mass after
chronic 2-adrenergic-receptor
blockade could be the result of decreases in muscle protein, because
2-adrenergic-receptor stimulation increases skeletal muscle protein content by increasing synthesis and/or decreasing degradation (30). In the present study, we measured medial gastrocnemius total and myofibrillar protein
concentrations and found that they were unchanged after 14 days of
chronic 2-adrenergic-receptor
blockade (Table 2). Furthermore, the ICI treatment did not affect the
immunohistochemically identified fiber sizes in the plantaris. These
results suggest that although
2-adrenergic-agonist treatment
does promote skeletal muscle hypertrophy (10, 30),
2-adrenergic receptors may not play an obligatory role in maintaining muscle mass in the present conditions.
We have previously observed that the oxidative capacity of skeletal
muscle is unchanged in fast muscles but is slightly increased in the
soleus, a slow muscle, after chronic
2-adrenergic-receptor stimulation (16). This is consistent with a fiber type transformation from slow to fast (31), because type IIa fibers are more oxidative than
are type I fibers in the rat (6). Benbachir-Lamrini and collaborators
(1) did not observe a change in soleus muscle oxidative or glycolytic
capacity after chronic
2-adrenergic-receptor blockade.
Similarly, in the present study, chronic blockade of 2-adrenergic receptors did not
modify the oxidative potential of any of the muscles studied (Table 2),
nor did it cause a fiber type transformation in the plantaris. Because
the present treatment did not result in significant changes in skeletal
muscle mass, protein concentration, oxidative potential, fiber type, or
fatigue resistance,
2-adrenergic-receptor
stimulation does not appear to be necessary for maintenance of these
characteristics, at least not for 14 days under these conditions. It
could be argued that -blockade was insufficient to promote these
changes, but this is unlikely because -adrenergic-receptor
upregulation occurred.
Indeed, the 14-day treatment with ICI resulted in an upregulation of
-adrenergic receptors in the lateral gastrocnemius muscle (42%;
Fig. 3). This upregulation of receptors is an expected response after
chronic treatment with a blocker (21). Few researchers have studied the
implications of receptor number on skeletal muscle tissue
responsiveness. The treatment could cause a heightened responsiveness
of skeletal muscle to catecholamines after abrupt withdrawal of ICI.
Such a hypersensitivity has been observed in other tissues after
treatment with a -blocker (18). In this study, the relative (g/g;
Fig. 1) and absolute (kg; Fig. 2) isometric contractile forces of the
medial gastrocnemius muscle were increased after a chronic ICI
treatment and a washout period. Twitch and tetanic forces were
increased. These increases in force were reproducible and could not be
explained by factors such as muscle or body temperature. These results
suggest that tetanic force under normal in situ conditions may not be
maximal and are supported by reports of increased tetanic forces
(maximal tetanic force/unit area) after different treatments (13,
15). Furthermore, our results, obtained by using acute
administration of ICI to control animals (Table 3), suggest that under
normal in situ conditions,
2-adrenergic-receptor stimulation may be involved in the production of maximal contractile forces.
Several possible causes for the increased forces after chronic ICI treatment were evaluated. Chronic ICI treatment might have facilitated neuromuscular transmission at higher frequencies by some unknown mechanism. We believe that this possibility is unlikely. For example, rat motor units stimulated at 200 Hz show initial electromyographic amplitudes, reflecting the number of recruited fibers in the unit, similar to those seen during a single twitch, and are capable of maintaining this amplitude beyond the time required for the generation of peak tetanic force (11). This would suggest that all fibers of tetanically stimulated control muscles were maximally activated at the time that peak tetanic forces were measured in the present study. In addition, direct and indirect muscle stimulation resulted in similar twitch and tetanic forces. Our results clearly demonstrate that, in the present model and under the conditions of the model, recruitment of muscle fibers is not submaximal. This shows that the increased forces in the ICI-treated animals are due to increases in the tension generated by the muscle fibers and are not secondary to increased recruitment.
Next, ICI or a metabolite of the drug could directly or indirectly increase the muscle's contractile forces. This hypothesis was eliminated because in experiments in which ICI was infused via the jugular vein or administered acutely subcutaneously to control animals before or during the measurement of contractile properties, no increase in contractile force was observed (Table 3).
Increases in myofibrillar proteins could also explain the elevated
forces in the ICI-treated group. However, as demonstrated in the medial
gastrocnemius, total and myofibrillar protein concentrations did not
change in response to the treatment (Table 2). Therefore, the
contractile force increases were not due to changes in muscle protein
content or concentration. Another possible explanation for the
increased contractile forces is a fiber type transformation. Indeed, a
slow-to-fast transformation might result in increased muscle forces, as
demonstrated with fiber-specific force (2). However, this
type of transformation, from type I to IIa to IIb, occurs after chronic
treatment with a 2-adrenergic
agonist (31) and, to our knowledge, has not been reported after a
treatment with a 2-adrenergic
antagonist. The fiber type transformation after agonist treatment is
accompanied by an increase in oxidative potential in slow muscle (16),
which we did not observe in this study (Table 2). Our experiments in
which we used myosin heavy chain antibodies also did not indicate fiber
type transformations in the plantaris muscle after chronic
2-blockade. Therefore, a fiber
type transformation is unlikely to be the mechanism responsible for the
increased forces.
When chronic
2-adrenergic-receptor blockade
was followed by an acute injection of ICI 2-3 h before measurement
of contractile properties, contractile forces returned to control
values (Figs. 1 and 2) despite the fact that -adrenergic-receptor
density of the lateral gastrocnemius was also elevated in these
animals. Therefore, the larger contractile forces of the ICI-treated
group subjected to a washout period are likely to have been mediated by
stimulation of 2-adrenergic
receptors, presumably by endogenous catecholamines.
A lengthening of the twitch duration could explain the increased twitch force. However, we did not observe any change in twitch contractile time or in the half relaxation time in ICI-treated animals (Table 1). In experiments in which the muscle's cAMP content was increased with dibutyryl cAMP, there was an increase in twitch duration in the medial gastrocnemius muscle (Table 3). In these experiments, twitch forces were also increased slightly, but we were unable to replicate the increases in tetanic forces observed in the chronically blocked group. This may reflect a diffusion problem of the drug in whole muscles, or it could suggest that the mechanism responsible for increasing tetanic forces of the ICI-treated animals may not be solely dependent on the accumulation of cAMP.
Another possible cause for the increased forces is an
increased intracellular calcium concentration.
2-Adrenergic-receptor stimulation by endogenous catecholamines could increase cytosolic calcium concentration during activation as a result of increased release from the sarcoplasmic reticulum (3). Twitch and tetanic forces
have been shown to be potentiated by >50 and 10-20%,
respectively, when cytosolic calcium concentrations are increased by
using caffeine (7). The increased forces we observed after the ICI
treatment and withdrawal in the present study are very similar to the
percentages reported by Fryer and Neering (7), who used caffeine in
their study. However, we were unable to potentiate the tetanic forces in our experiments with caffeine, although twitch force was
consistently increased (Table 3). The caffeine infused may not have
been sufficient to increase tetanic force, but in the present in situ
preparations we were unable to use higher caffeine doses.
In summary, this study demonstrates that a chronic treatment with ICI
did not modify several skeletal muscle characteristics, including mass,
protein concentration, fiber type percentages, and oxidative potential,
suggesting that regular activation of these receptors is not necessary
for tissue maintenance of those characteristics. Furthermore, we show
that fast skeletal muscle -adrenergic receptors are upregulated in
response to chronic 2-adrenergic blockade and that
this upregulation increases isometric contractile forces. To our
knowledge, this is the first evidence demonstrating that upregulation
of skeletal muscle -adrenergic receptors is associated with
increases in muscle contractile force. These are important findings
because they demonstrate that under normal in situ conditions, muscle
tetanic force may not be maximal. The inotropic responses could be due
to increased calcium concentrations in the cytoplasm during skeletal
muscle activation. More research is needed to determine the exact
mechanism(s) involved in these responses.
ACKNOWLEDGEMENTS
The contributions of Drs. F. Péronnet (Université de Montréal) and F. Trudeau (Université du Québec à Trois-Rivières) are gratefully acknowledged.
FOOTNOTES
Address for reprint requests: L. Béliveau, Université de Montréal, Département d'Éducation Physique, C.P. 6128, Succursale Centre-ville, Montréal, PQ, Canada H3C 3J7 (E-mail: BELIVEL{at}ere.UMontreal.ca).
Received 9 October 1996; accepted in final form 8 April 1997.
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