| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Centre for Activity and Ageing, School of Kinesiology, and 2 Department of Physiology, The University of Western Ontario, London, Ontario N6A 3K7; and 3 Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Carbonic anhydrase (CA) inhibition is associated with a
lower plasma lactate concentration
([La
]pl),
but the mechanism for this association is not known. The effect of CA
inhibition on muscle high-energy phosphates [ATP and
phosphocreatine (PCr)], lactate
([La]m),
and glycogen was examined in seven men [28 ± 3 (SE) yr]
during cycling exercise under control (Con) and acute CA inhibition
with acetazolamide (Acz; 10 mg/kg body wt iv). Subjects performed 6-min step transitions in work rate from 0 W to a work rate corresponding to
~50% of the difference between the
O2 uptake at the ventilatory threshold and peak O2 uptake.
Muscle biopsies were taken from the vastus lateralis at rest, at 30 min
postinfusion, at end exercise (EE), and at 5 and 30 min postexercise.
Arterialized venous blood was sampled from a dorsal hand vein and
analyzed for
[La]pl.
ATP was unchanged from rest values; no difference between Con and Acz
was observed. The fall in PCr from rest [72 ± 3 and 73 ± 3.6 (SE) mmol/kg dry wt for Con and Acz, respectively] to EE (51 ± 4 and 46 ± 5 mmol/kg dry wt for Con and Acz, respectively) was similar in Con and Acz. At EE, glycogen (mmol glucosyl units/kg dry
wt) decreased to similar values in Con and Acz (307 ± 16 and 300 ± 19, respectively). At EE, no difference was observed in [La]m
between conditions (46 ± 6 and 43 ± 5 mmol/kg dry wt for Con and Acz, respectively). EE
[La]pl
was higher during Con than during Acz (11.4 ± 1.0 vs. 8.2 ± 0.6 mmol/l). The similar
[La]m
but lower
[La]pl
suggests that the uptake of
La by other tissues is
enhanced after CA inhibition.
muscle lactate; plasma lactate; high-energy phosphates; carbonic anhydrase
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
THE PHYSIOLOGICAL SIGNIFICANCE of erythrocyte carbonic
anhydrase (CA I and CA II) in the removal of
CO2 from the body under resting
and exercise conditions has been studied extensively (for review see
Ref. 26); however, relatively little is known about the role of CA in
muscle metabolism in humans. During exercise, CA inhibition with
acetazolamide (Acz) results in a lower plasma lactate
(La) concentration
([La]pl)
during maximal (13, 14) and submaximal exercise (7, 18, 21) compared
with the uninhibited condition. Muscle
La content
([La]m)
was not affected by chronic Acz administration during exercise in
humans (18); in horses, Acz administration was associated with a lower
[La]m
immediately after maximal exercise (20). A confounding factor in these
previous studies (18, 20) was that Acz was administered chronically
over 3 days and resulted in a metabolic acidosis before the onset of
exercise, a condition that has been shown to inhibit muscle
glycogenolysis and impair
La efflux from muscle (25).
In addition, in the study of Rose et al. (20), muscle glycogen content
was significantly reduced before the start of exercise and may have
contributed to the lower rate of glycogenolysis and
La production (11) in their study.
Acz administered acutely by infusion is not associated with a
significant acidosis before the onset of exercise (13, 21) and offers
an opportunity to study the effect of CA inhibition alone, without the
confounding effect of acidosis. Using a protocol of acute CA
inhibition, we demonstrated that
[La]pl
was reduced during moderate- and heavy-intensity, constant-load exercise, independent of the initial plasma acid-base status (21). The
effect of Acz-induced CA inhibition on muscle metabolism in the absence
of a significant extracellular acidosis, to our knowledge, has not been
examined previously. Therefore, the purpose of the present study was to
examine the effect of acute Acz-induced CA inhibition on specific
muscle metabolites and
[La]pl
during heavy-intensity, constant-load exercise to determine the
mechanism responsible for the lower
[La]pl
typically observed after Acz administration. We hypothesized that the
lower
[La]pl
observed after CA inhibition would be associated with an inhibition of
glycogen breakdown and pyruvate
(Pyr) production.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Subjects. Seven healthy men participated in the study. The experimental protocol and all possible risks associated with participation in the study were outlined, and informed consent was obtained from each subject. Approval for this study was granted by The University of Western Ontario Review Board for Health Sciences Research Involving Human Subjects.
General protocol.
Each subject underwent preliminary testing for the determination of
ventilatory threshold
(
ET) and
peak O2 uptake
(O2 peak) with use of
a ramp forcing function (25 W/min) to volitional fatigue on an
electromagnetically braked cycle ergometer (model H-300-R, Lode). The
highest O2 uptake
(O2) averaged over 20-s
intervals was taken as
O2 peak. The
ET was
determined as the O2 at which the ventilatory equivalent for
O2
(E/O2)
and end-tidal PO2
(PETO2) increased with no
concomitant increase in the ventilatory equivalent for
CO2 output
(E/CO2)
or decrease in end-tidal PCO2
(PETCO2). The work rate
performed during the constant-load test was estimated to elicit a
O2 that was ~50% of the
difference between the O2
at the ET
and O2 peak: ET + [(O2 peak 
ET) · 0.5].
The square-wave transition, which was 6 min in duration, was followed
by 30 min of supine recovery.
12 h before testing. Subjects were asked not to engage
in any heavy-intensity exercise for 3 days before testing but were
allowed to follow their normal activity schedule. The exercise tests
were performed at the same time of the day for each subject. Exercise
tests were separated by 2-3 wk.
On each occasion, subjects rested supine while a percutaneous Teflon
catheter (21-gauge Angiocath) was placed into a dorsal hand vein. Blood
was arterialized by wrapping the hand and forearm in a heating pad. The
Bergström technique (4) was used to prepare subjects for biopsies
of the vastus lateralis muscle. The skin overlying the biopsy site in
each leg was initially prepared using local anesthetic (2% lidocaine).
A small incision was made through the skin and underlying fascia of
each leg to facilitate rapid sampling during testing. The incisions
were covered with sterile gauze, except before muscle samples were obtained.
After 15 min of rest, a blood sample was drawn for baseline measures,
then the subject either rested for 30 min (Con studies) or was infused
with Acz (10 mg/kg iv over a 3-min period) and then rested for 30 min
(Acz studies). Breath-by-breath measurements of gas exchange and
ventilation were made during loadless cycling and during the last
minute of exercise. Blood samples were obtained during each of the two
conditions at rest, at 30 min postinfusion, during loadless cycling, at
end-exercise, and at specific times during recovery (5, 10, 15, 20, 25, and 30 min).
Muscle samples were obtained at rest, at 30 min postinfusion,
immediately after exercise, and at 5 and 30 min of recovery. Muscle
samples corresponding to pre- and postinfusion were obtained while the
subject rested in the supine position. End-exercise muscle samples were
obtained within 5 s of the end of exercise while the subjects remained
seated on the cycle ergometer. Subjects were returned to the supine
position during recovery. Immediately after the muscle samples were
obtained, the biopsy needles were plunged into liquid nitrogen;
~5-7 s elapsed between the time the samples were obtained and
the time they were frozen. The tissue was stored at 80°C for
later analysis.
Materials and methods.
Inspired and expired volumes were measured by a low-resistance,
low-dead space (90 ml) bidirectional turbine and volume transducer (model VMM-110, Alpha Technologies). The volume signal was calibrated before each test with a syringe of known volume (990 ml). Respired gases were sampled continuously at the mouth (1 ml/s) by a mass spectrometer (model MGA-1100, Perkin-Elmer) for determination of the
fractional concentrations of O2,
CO2,
and N2. The mass spectrometer was calibrated with precision-analyzed gas mixtures before
each test. The analog signals from the mass spectrometer and turbine
transducer were sampled every 20 ms and stored on the computer hard
disk for later analysis. Breath-by-breath computations for
O2,
CO2,
E,
PETO2, and
PETCO2 were performed after
correction for delays in the sampling capillary and analysis system and
for fluctuations in lung gas stores by computer algorithms (3).
Corrections for temperature and water vapor were made for conditions
measured near the mouth. Heart rate was monitored continuously using an
electrocardiograph, with electrodes placed in a modified
V5 configuration.
20 min). Whole blood (200 µl) was analyzed (at
37°C) for plasma pH {H+
concentration
([H+])},
PCO2, and
[La]pl
with use of selective electrodes (StatProfile 9 Plus Blood Gas-Electrolyte Analyzer, Nova Biomedical Canada). The electrodes were
calibrated before each test and at regular intervals during analysis.
Plasma HCO3 concentration
([HCO3]) was calculated
from measured pH and PCO2.
Muscle metabolite concentrations of glycogen ([glycogen]),
ATP ([ATP]), PCr ([PCr]),
Pi
([Pi]), creatine
([Cr]),
[La], and
Pyr
([Pyr]) were
determined fluorometrically (model 450, Sequoia-Turner) from
freeze-dried tissue according to established procedures (10). Muscle
metabolites were adjusted to the highest total creatine (TCr = PCr + Cr) in each condition (Con vs. Acz) for each subject to correct for any
contamination by blood and connective tissue. There was no significant
difference in TCr; the mean correction required was 3.4%, with a range
of 0.06-12.8%.
Statistics. Gas exchange, plasma, and muscle data were analyzed using a two-way repeated-measures ANOVA with condition (Con vs. Acz) and time as the main effects. When condition was not a factor, data were analyzed using a one-way repeated-measures ANOVA. A significant F ratio was further analyzed using Student-Newman-Keuls post hoc analysis. Statistical significance was accepted at P < 0.05. Values are means ± SE.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Subjects.
The physical characteristics, peak values for the ramp exercise test,
and constant-load exercise work rates for each subject are presented in
Table 1. Gas exchange data are reported for only five subjects because of technical difficulties with the gas
analysis system.
|
O2,
CO2, heart rate, and
E.
The effects of CA inhibition with an acute infusion of Acz on gas
exchange and E
are presented in Fig. 1.
O2 was not affected by CA
inhibition during loadless cycling (904 ± 87 and 865 ± 87 ml/min for Con and Acz, respectively) or at end exercise (3,426 ± 266 and 3,332 ± 334 ml/min for Con and Acz, respectively). Heart rate (not shown) was not affected in Acz studies during loadless cycling or at end exercise. During loadless cycling,
CO2 was similar between Con
and Acz (775 ± 58 and 800 ± 72 ml/min, respectively) conditions; end-exercise CO2
was lower (P < 0.05) during Acz than
during Con (3,542 ± 340 vs. 3,812 ± 323 ml/min). CA inhibition resulted in a higher (P < 0.05)
E during
loadless cycling (18.7 ± 1.2 and 21.8 ± 1.5 l/min for Con and
Acz, respectively) and at end exercise (111.4 ± 13.1 and
127.3 ± 15.3 l/min for Con and Acz, respectively).
E/O2
and
E/CO2
were higher (P < 0.05) in Acz than
in Con during loadless cycling; this difference was attributed to the
higher
E in
the Acz studies. End-exercise E/O2
and
E/CO2
were higher during Acz than during Con consequent to the
higher E
and lower CO2 during Acz
administration.
|
Plasma acid-base status and La.
The effects of CA inhibition with an acute infusion of Acz on acid-base
status in equilibrated plasma are presented in Fig. 2. Acz was administered acutely (30 min
before exercise) to avoid the development of a metabolic acidosis
before the onset of exercise. Plasma
[H+], determined 30 min postinfusion at rest, was not affected by an acute infusion of Acz
(36 ± 1 and 36 ± 1 nmol/l for Con and Acz, respectively; Fig.
2A). End-exercise plasma
[H+] increased
(P < 0.05) above rest values with no
difference between conditions. Plasma
[H+] returned to rest
values by 20 and 30 min of recovery in Con and Acz, respectively.
Resting plasma [HCO3] was
not affected by Acz infusion (Fig.
2B). Plasma
[HCO3] decreased
(P < 0.05) below rest
values during exercise in Con and Acz; end-exercise plasma
[HCO3] was higher (P < 0.05) in Acz than in Con (21 ± 1 vs. 19 ± 1 mmol/l). Plasma [HCO3] remained
below rest values throughout recovery with no differences between
conditions. Resting arterial PCO2
(PaCO2) was similar in Con and Acz (Fig.
2C).
PaCO2 decreased
(P < 0.05) below rest levels during
exercise in Con, but not until 5 min of recovery in Acz.
PaCO2 returned to preinfusion rest
values by 30 min of recovery in Acz but remained below rest values
throughout recovery in Con.
|
]pl
was similar in Con and Acz (Fig.
2D).
[La]pl
increased (P < 0.05) during exercise
in both conditions but was lower (P < 0.05) in Acz than in Con (8.2 ± 0.6 vs. 11.4 ± 1.0 mmol/l)
at end exercise.
[La]pl
remained lower (P < 0.05) in Acz
than in Con at 5 min of recovery but was similar between conditions for
the remainder of recovery; [La]pl
remained elevated (P < 0.05) above
rest values throughout recovery.
Muscle metabolites.
The effects of CA inhibition with an acute infusion of Acz on muscle
metabolites during exercise and recovery are presented in Fig.
3. Muscle [ATP] was not
affected by CA inhibition and remained unchanged from rest values
during exercise and recovery (Fig.
3A). Muscle [PCr]
decreased (P < 0.05) during
exercise, reaching similar values in Con and Acz (51 ± 4 and 46 ± 5 mmol/kg dry wt, respectively; Fig.
3B). The increase
(P < 0.05) in muscle [Cr] immediately postexercise was similar between Con and
Acz (63 ± 2 and 69 ± 4 mmol/kg dry wt, respectively)
and was of similar magnitude to the decrease in [PCr] (Fig.
3C). Muscle
[Pi] increased (P < 0.05) with exercise in Con and
Acz (51 ± 3 and 49 ± 4 mmol/kg dry wt, respectively), with no
difference between conditions. Muscle [PCr],
[Cr], and
[Pi] returned to rest
values by 5 min of recovery.
|
]m
increased (P < 0.05) during exercise
and reached similar end-exercise values (46 ± 6 and 43 ± 5 mmol/kg dry wt in Con and Acz, respectively); [La]m
remained elevated above rest levels throughout recovery (Fig. 3F). Although it was not
significant,
[La]m/[La]pl
(mmol · kg dry
wt1 · mmol1 · l1)
at end exercise tended to be higher (P = 0.075) in Acz than in Con (5.2 ± 0.3 vs. 4.1 ± 0.5; Fig.
4A).
Muscle [Pyr]
increased (P < 0.05) during exercise
to similar end-exercise values (0.565 ± 0.074 and 0.490 ± 0.083 mmol/kg dry wt in Con and Acz, respectively) and
returned to rest levels during recovery (Fig.
3G).
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
This study examined the effect of acute CA inhibition with Acz on
muscle metabolism during heavy-intensity, constant-load exercise. The
lower end-exercise
[La]pl
observed at a similar power output in Acz than in Con in the present
study is consistent with previous studies (12, 13, 21). However, this
is the first report describing muscle metabolic responses after acute
Acz-induced CA inhibition and indicates, contrary to our hypothesis,
that muscle glycogen breakdown and intramuscular
La accumulation were not
affected by Acz. These findings suggest that the lower
[La]pl
observed during exercise after Acz administration is not a result of an
inhibition of glycogenolysis and decreased muscle La production. These data,
in combination with previous findings demonstrating that
O2 kinetics (and presumably
pyruvate oxidation) at the onset of moderate- and heavy-intensity
constant-load exercise were similar in Acz and Con (21), suggest that
the lower
[La]pl
is due to an enhanced removal of
La by other
tissues, including erythrocytes, heart, liver, and moderately active
and inactive skeletal muscle.
To determine the effect of CA inhibition independent of the effects of
the metabolic acidosis that typically develops with prolonged Acz
administration (14, 27), exercise was initiated 30 min after an
intravenous infusion of Acz. Plasma
[H+], measured at
equilibrium, was not altered by CA inhibition during the 30-min
accommodation period, exercise, or recovery. CA activity was not
measured in the present study. However, it has been demonstrated previously that erythrocyte CA isozymes (CA I and CA II) are inhibited (>99.0%) at 5 mg/kg (~20 µmol/kg) of Acz (28). The dose of Acz
used in the present study was 10 mg/kg body wt (~45 µmol/kg; ~2.81 × 104 mol/l
for an 80-kg subject) administered intravenously 30 min before the
onset of exercise. Available information indicates that the half time
for Acz uptake by erythrocytes and skeletal muscle is 30-60 min at
104-106
mmol/l (8), and the plasma half-life for Acz is ~100 min (17). Thus
the plasma concentrations of Acz should be sufficiently high during the
duration of data collection to inhibit at least the erythrocyte isozymes.
Physiologically, the end-exercise
CO2 after Acz was lower and
the
PETCO2-PaCO2
gradient was negative and opposite to that found in Con, implying that
CO2 equilibration between blood
and alveolar gas was not achieved during transit through the pulmonary
capillaries. These effects may be related to the inhibition of lung CA,
which has been localized in the cytosolic space of lung epithelial (CA
II) and endothelial cells (CA I and CA II), as well as in association
with the intravascular surface of the endothelial cells (CA IV) (15,
16). However, the inhibition of CA associated with muscle on the
ability to eliminate CO2 has not
been established. CA is present in at least three forms in human
skeletal muscle: a sulfonamide-resistant cytosolic isozyme (CA III)
found primarily in slow-twitch oxidative fibers, a
sulfonamide-sensitive cytosolic isozyme (CA II) found in fast-twitch
oxidative fibers, and a membrane-bound sulfonamide-sensitive isozyme
(CA IV) found on the sarcolemma and sarcoplasmic reticulum (24).
Recently, the presence of a membrane-bound CA IV has been identified in the intravascular space of muscle capillaries in humans (22). The
physiological responses suggest that the acute infusion of Acz
functionally inhibited the erythrocyte CA isozymes and, presumably, the
sarcolemmal and endothelial CA isozymes, if it is assumed that
equilibrium is reached between the interstitial fluid and the plasma
Acz concentration. However, because Acz is relatively membrane
impermeable (8) and the cytosolic CA III is relatively insensitive to
sulfonamides, it is doubtful that the intracellular CA III isozyme was
inhibited within the 70-min period over which data were collected in
this study.
Acz administration did not affect glycogen utilization or the
accumulation of muscle La
or Pyr over the duration of
exercise examined in this study. This finding is in contrast to that of
Rose et al. (20), who reported that, in horses exercising maximally,
muscle glycogen depletion and muscle
La accumulation were
depressed after Acz administration. In that study the higher dose of
Acz (i.e., 30 mg/kg) and/or the chronic administration of Acz,
resulting in a lower muscle pH at rest and greater
CO2 retention during exercise, led
to a greater fall in muscle pH, which may have acted to inhibit
glycolysis.
NH4Cl-induced metabolic acidosis
has been shown to inhibit glycolysis and result in lower muscle and
plasma La (25), suggesting
that this effect is not specific to CA inhibition. In addition, the
muscle glycogen content before the start of exercise was reduced by
~30% in the Acz studies (20) and may also have contributed to the
lower rate of glycogenolysis and
La accumulation (11). A
depression of muscle glycogenolysis was not observed after Acz
treatment in the present study, possibly because muscle pH was not
affected by Acz or glycolytic flux was maintained, despite
a fall in muscle pH, subsequent to allosteric modification of enzyme
activity (6). Interestingly, chronic, compared with acute, Acz
administration in humans results in a further reduction in
[La]pl
(13, 14), which may be consequent to impaired glycolysis caused by the
induced metabolic acidosis, although this has not been established.
[La]pl
reflects a balance between
La efflux from the
exercising muscle and the uptake of
La by other tissues,
including erythrocytes, heart, liver, and moderately active and
inactive skeletal muscle. Although it has not been determined in the
present study, a greater uptake of
La from the plasma by
inactive muscles may have contributed to the lower
[La]pl
found with Acz administration. However, the Acz dose and protocol used
in this study were similar to those used by Kowalchuk et al. (13), who
demonstrated a lower arterial
[La] and
arterial-venous
[La] difference
in Acz but fractional removal of
La across an inactive
forearm similar to Con, suggesting that
La uptake was related to
the arterial
[La]. These
data would suggest that La
uptake by other tissues would be attenuated during the Acz treatment. Although La uptake by the
inactive muscle was determined by the arterial-venous La difference, blood flow
was not determined in that study (13). The importance of blood flow in
the uptake of La by
inactive muscles has recently been demonstrated by Bangsbo et al. (1).
They reported that La
uptake by inactive muscle was higher with increasing blood flows, despite a similar arterial-venous
La difference between
conditions. The effect of Acz on muscle blood flow during exercise is
not known. Although end-exercise
PETCO2 was lower in Acz, the
equilibrated PaCO2 tended to be higher
in Acz, although these differences were not significant (Fig.
2C). Thus, as a consequence of the
disequilibrium that exists in the CO2 system after CA inhibition, it
is possible that a higher PaCO2 existed
in the peripheral vasculature, resulting in greater vasodilation.
The removal of La by the
erythrocytes may have been enhanced after Acz administration, thereby
contributing to the lower
[La]pl
but similar
[La]m
observed during Acz. The movement of
La across the erythrocyte
membrane occurs via 1) the nonionic
diffusion of undissociated lactic acid,
2) an anionic exchange involving the
band 3 system, or 3) cotransport
with an H+ via a specific
monocarboxylate transporter (for review see Refs. 9 and 19). Whether
Acz administration affects these transport mechanisms or the extent to
which they may affect the movement of
La across cell membranes is
not known and deserves further attention. However, in vivo examination
of these transport mechanisms after CA inhibition is complicated by the
disequilibrium that exists in the
CO2 system as blood moves through
the circulatory system, and, therefore, determining the intra- and
extracellular pH gradients that affect
La movement across cell
membranes would be difficult during whole body exercise.
The
[La]m/[La]pl
(mmol · kg1 · mmol1 · l1)
was not significantly different between Acz and Con conditions at end
exercise (Fig. 4A).
[La]m/[La]pl
(Fig. 4B) was also calculated
assuming that 1) intracellular water
content in resting muscle was 290 ml intracellular water/100 g tissue
dry wt (23) and 2) CA inhibition did
not affect the distribution of water between body compartments.
Although chronic Acz administration is associated with a significant
redistribution of water between tissue compartments (as determined by
an increase in hematocrit, a decrease in extracellular water content,
and an increase in intracellular water content) (5), we did not observe
any difference in hematocrit between conditions before the start of
exercise (data not presented), suggesting that a significant
redistribution of water between compartments had not occurred as a
consequence of the acute Acz administration protocol. The similar
[La]m/[La]pl
supports the hypothesis that
La uptake from the muscle
was enhanced by other tissues after Acz administration.
Inhibition of CA with an acute infusion of Acz did not affect
O2 during loadless cycling or
at end exercise. Recent results from our laboratory (21) have
demonstrated that end-exercise O2 and the kinetics of
O2 to and from a step
increase to moderate- and heavy-intensity constant-load exercise were
not different, despite a lower
[La]pl
during acute Acz administration. Because oxidative phosphorylation does
not meet the total energy requirements during the transition to a
higher exercise intensity (i.e.,
O2 deficit), the breakdown of PCr
and increase in anaerobic glycolysis must provide the balance of energy
necessary for maintaining ATP turnover. Although the similar
O2 kinetics in Con and Acz
suggested that the kinetics of PCr breakdown (2) and muscle
La production would also be
similar, the contributions of these energy pathways to the energy
demands were not determined (21). In the present study the fall in
muscle [PCr] and the increase in
[Pi] and
[Cr] during exercise were similar in Con and Acz. During
recovery, muscle [PCr],
[Pi], and
[Cr] returned to rest values by 5 min of recovery with no
difference between conditions. In addition, changes in
[La]m
and [Pyr]
during exercise and recovery were similar between conditions. To our
knowledge PCr and Pi kinetics
during the on- or off-transients of exercise have not been determined
during Acz administration, but it is expected that the kinetics would
not be affected by Acz administration given the similarity of
O2 kinetics during the on-
and off-transients of exercise found previously (21). Thus it would
appear, on the basis of comparable metabolic changes between Acz and
Con during the transition to and from exercise and in steady-state
exercise that were observed in this and other studies (21), that muscle
energetics associated with the on- and off-transition to and from
heavy-intensity constant-load exercise were not affected by acute CA inhibition.
In summary, this study examined the effect of acute CA inhibition with
a single infusion of Acz on muscle metabolism and plasma acid-base
changes during heavy-intensity constant-load exercise and recovery. Acz
administration was associated with similar muscle glycogen breakdown
and muscle La accumulation
and a lower
[La]pl
immediately after exercise and in recovery. The removal of La from the plasma by other
tissues during exercise may be enhanced after CA inhibition, thereby
contributing to the lower
[La]pl
in the Acz treatment.
| |
ACKNOWLEDGEMENTS |
|---|
The authors thank the participants who took part in the study. The technical support of Brad Hansen is greatly appreciated. The authors are greatly indebted to Margaret Ball-Burnett and Susan Grant (University of Waterloo) for use of their biopsy needles and their assistance in the analysis of muscle tissue.
| |
FOOTNOTES |
|---|
Financial support was provided by an operating grant from the Natural Sciences and Engineering Research Council of Canada. B. W. Scheuermann was supported by a Natural Sciences and Engineering Research Council of Canada Graduate Scholarship.
This research was carried out at The Centre for Activity and Ageing (affiliated with the Faculty of Health Sciences, School of Kinesiology, and the Faculty of Medicine at The University of Western Ontario and The Lawson Research Institute at St. Joseph's Health Centre).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: J. M. Kowalchuk, School of Kinesiology, Thames Hall, The University of Western Ontario, London, ON, Canada N6A 3K7 (E-mail: jkowalch{at}julian.uwo.ca).
Received 19 June 1998; accepted in final form 14 October 1999.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Bangsbo, J.,
T. Aagaard,
M. Olsen,
B. Kiens,
L. P. Turcotte,
and
E. A. Richter.
Lactate and H+ uptake in inactive muscles during intense exercise in man.
J. Physiol. (Lond.)
488:
219-229,
1995
2.
Barstow, T. J.,
S. Buchthal,
S. Zanconato,
and
D. M. Cooper.
Muscle energetics and pulmonary oxygen uptake kinetics during moderate exercise.
J. Appl. Physiol.
77:
1742-1749,
1994
3.
Beaver, W. L.,
N. Lamarra,
and
K. Wasserman.
Breath-by-breath measurement of true alveolar gas exchange.
J. Appl. Physiol.
51:
1662-1675,
1981
4.
Bergström, J.
Muscle electrolytes in man.
Scand. J. Clin. Lab. Invest.
14, Suppl. 68:
1-110,
1962.
5.
Brechue, W. F.,
J. M. Stager,
and
H. C. Lukaski.
Body water and electrolyte responses to acetazolamide in humans.
J. Appl. Physiol.
69:
1397-1401,
1990
6.
Connett, R. J.,
and
K. Sahlin.
Control of glycolysis and glycogen metabolism.
In: Handbook of Physiology. Exercise: Regulation and Integration of Multiple Systems. Bethesda, MD: Am. Physiol. Soc, 1996, sect. 12, chapt. 19, p. 870-911.
7.
Davies, S. F.,
C. Iber,
S. A. Keene,
C. D. McArthur,
and
M. J. Path.
Effect of respiratory alkalosis during exercise on blood lactate.
J. Appl. Physiol.
61:
948-952,
1986
8.
Geers, C.,
and
G. Gros.
Inhibition properties and inhibition kinetics of an extracellular carbonic anhydrase in perfused skeletal muscle.
Respir. Physiol.
56:
269-287,
1984[Web of Science][Medline].
9.
Gladden, L. B.
Lactate transport and exchange during exercise.
In: Handbook of Physiology. Exercise: Regulation and Integration of Multiple Systems. Bethesda, MD: Am. Physiol. Soc, 1996, sect. 12, chapt. 14, p. 614-648.
10.
Green, H. J.,
J. R. Sutton,
P. Young,
A. Cymerman,
and
C. S. Houston.
Operation Everest II: muscle energetics during maximal exhaustive exercise.
J. Appl. Physiol.
66:
142-150,
1989
11.
Hargreaves, M.,
G. McConell,
and
J. Proietto.
Influence of muscle glycogen on glycogenolysis and glucose uptake during exercise in humans.
J. Appl. Physiol.
78:
288-292,
1995
12.
Korotzer, B.,
T. Jung,
W. Stringer,
P. Nguyen,
A. Jones,
and
K. Wasserman.
Effect of acetazolamide on lactate, lactate threshold, and acid-base balance during exercise (Abstract).
Am. J. Respir. Crit. Care Med.
155:
A171,
1997.
13.
Kowalchuk, J. M.,
G. J. F. Heigenhauser,
J. R. Sutton,
and
N. L. Jones.
The effect of acetazolamide on gas exchange and acid-base control after maximal exercise.
J. Appl. Physiol.
72:
278-287,
1992
14.
Kowalchuk, J. M.,
G. J. F. Heigenhauser,
J. R. Sutton,
and
N. L. Jones.
The effect of chronic acetazolamide administration on gas exchange and acid-base control after maximal exercise.
J. Appl. Physiol.
76:
1211-1219,
1994
15.
Lönnerholm, G.
Carbonic anhydrase in the lung.
Acta Physiol. Scand.
108:
197-199,
1980[Web of Science][Medline].
16.
Lönnerholm, G.
Pulmonary carbonic anhydrase in the human, monkey, and rat.
J. Appl. Physiol.
52:
352-356,
1982
17.
Maren, T. H.
The relation between enzyme inhibition and physiological response in the carbonic anhydrase system.
J. Pharmacol. Exp. Ther.
139:
140-153,
1963
18.
McLellan, T.,
I. Jacobs,
and
W. Lewis.
Acute altitude exposure and altered acid-base states. II. Effects on exercise performance and muscle and blood lactate.
Eur. J. Appl. Physiol.
57:
445-451,
1988.
19.
Poole, R. C.,
and
A. P. Halestrap.
Transport of lactate and other monocarboxylates across mammalian plasma membranes.
Am. J. Physiol. Cell Physiol.
264:
C761-C782,
1993
20.
Rose, R. J.,
D. R. Hodgson,
T. B. Kelso,
L. J. McCutcheon,
W. M. Bayly,
and
P. D. Gollnick.
Effects of acetazolamide on metabolic and respiratory responses to exercise at maximal O2 uptake.
J. Appl. Physiol.
68:
617-626,
1990
21.
Scheuermann, B. W.,
J. M. Kowalchuk,
D. H. Paterson,
and
D. A. Cunningham.
Oxygen uptake kinetics following acute acetazolamide administration during moderate and heavy exercise.
J. Appl. Physiol.
85:
1384-1393,
1998
22.
Sender, S.,
G. Gros,
A. Waheed,
G. S. Hageman,
and
W. S. Sly.
Immunohistochemical localization of carbonic anhydrase IV in capillaries of rat and human skeletal muscle.
J. Histochem. Cytochem.
42:
1229-1236,
1994[Abstract].
23.
Sjogaard, G.,
and
B. Saltin.
Extra- and intracellular water spaces in muscles of man at rest and with dynamic exercise.
Am. J. Physiol. Regulatory Integrative Comp. Physiol.
243:
R271-R280,
1982
24.
Sly, W. S.,
and
P. Y. Hu.
Human carbonic anhydrases and carbonic anhydrase deficiencies.
Annu. Rev. Biochem.
64:
375-401,
1995[Web of Science][Medline].
25.
Sutton, J. R.,
N. L. Jones,
and
C. J. Toews.
Effect of pH on muscle glycolysis during exercise.
Clin. Sci. (Colch.)
61:
331-338,
1981[Medline].
26.
Swenson, E. R.
Kinetics of oxygen and carbon dioxide exchange.
In: Advances in Comparative and Environmental Physiology, edited by R. G. Boutilier. Berlin: Springer-Verlag, 1990, p. 163-210.
27.
Swenson, E. R.,
and
T. H. Maren.
A quantitative analysis of CO2 transport at rest and during maximal exercise.
Respir. Physiol.
35:
129-159,
1978[Web of Science][Medline].
28.
Wistrand, P. J.
The importance of carbonic anhydrase B and C for the unloading of CO2 by the human erythrocyte.
Acta Physiol. Scand.
113:
417-426,
1981[Web of Science][Medline].
This article has been cited by other articles:
|
|
 |
|
  A. M. Jonk, I. P. van den Berg, I. M. Olfert, D. W. Wray, T. Arai, S. R. Hopkins, and P. D. Wagner Effect of acetazolamide on pulmonary and muscle gas exchange during normoxic and hypoxic exercise J. Physiol., March 15, 2007; 579(3): 909 - 921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Wetzel, A. Hasse, S. Papadopoulos, J. Voipio, K. Kaila, and G. Gros Extracellular carbonic anhydrase activity facilitates lactic acid transport in rat skeletal muscle fibres J. Physiol., March 15, 2001; 531(3): 743 - 756. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Kowalchuk, S. A. Smith, B. S. Weening, G. D. Marsh, and D. H. Paterson Forearm muscle metabolism studied using 31P-MRS during progressive exercise to fatigue after Acz administration J Appl Physiol, July 1, 2000; 89(1): 200 - 209. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
