Department of Kinesiology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
To determine the influence of
a diuretic-induced reduction in plasma volume (PV) on substrate
turnover and oxidation, 10 healthy young males were studied during 60 min of cycling exercise at 61% peak oxygen uptake on two separate
occasions 1 wk apart. Exercise was performed under control
conditions (CON; placebo), and after 4 days of diuretic administration
(DIU; Novotriamazide; 100 mg triamterene and 50 mg
hydrochlorothiazide). DIU resulted in a calculated reduction of
PV by 14.6 ± 3.3% (P < 0.05). Rates of glucose
appearance (Ra) and disappearance (Rd) and
glycerol Ra were determined by using primed
constant infusions of [6,6-2H]glucose and
[2H5]glycerol, respectively. No differences
in oxygen uptake during exercise were observed between trials. Main
effects for condition (P < 0.05) were observed for
plasma glucose and glycerol, such that the values observed for DIU were
higher than for CON. No differences were observed in plasma
lactate and serum free fatty acid concentrations either at rest or
during exercise. Hypohydration led to lower (P < 0.05)
glucose Ra and Rd at rest and at 15 and 30 min
of exercise, but by 60 min, the effects were reversed
(P < 0.05). Hypohydration had no effect on rates of
whole body lipolysis or total carbohydrate or fat oxidation. A main
effect for condition (P < 0.05) was observed for
plasma glucagon concentrations such that larger values were observed
for DIU than for CON. A similar decline in plasma insulin occurred with
exercise in both conditions. These results indicate that
diuretic-induced reductions in PV decreases glucose kinetics during
moderate-intensity dynamic exercise in the absence of changes in total
carbohydrate and fat oxidation. The specific effect on glucose kinetics
depends on the duration of the exercise.
glucose turnover; glycerol turnover; lipolysis; stable isotopes
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
REDUCTIONS IN PLASMA VOLUME (PV), as incurred during hypohydration, pose potentially serious consequences to cardiovascular and thermoregulatory stability during prolonged exercise (36). Even small reductions in PV can increase cardiovascular strain and core temperature (5). If the loss exceeds a critical threshold, blood flow to the cutaneous circulation and sweat rates are impaired and cardiac output and arterial blood pressure may fall (11, 14, 15).
In an attempt to protect cardiovascular integrity and fluid and
electrolyte balance during exercise, increased activation of the
sympathetic nervous system (SNS) occurs, which results in elevated
blood concentrations of norepinephrine (NE), as a result of spillover
from the nerve endings, and epinephrine (Epi), secreted from the
adrenal medulla (38). Changes in SNS activation are also
accompanied by increased levels of plasma renin activity, aldosterone,
arginine vasopressin, and a decreased level of -atrial natriuretic
peptide (6, 38). Collectively, the major effects of these
hormonal changes during exercise are to increase electrolyte and water
reabsorption from the kidney, reduce sweat rates, and promote cardiac
contractility and vasoconstriction in the cutaneous and splanchnic
vasculature (6, 38). If the hypohydration is so severe as
to result in a lower cardiac output compared with euhydration,
increases in systemic vascular resistance occur (14, 18),
probably in conjunction with reductions in blood flow to the working
muscles (29).
The compensatory responses to hypohydration and exercise, both cardiovascular and hormonal, suggest that a shift in substrate turnover and oxidation may occur. The exaggerated increase in catecholamine concentration, particularly Epi, as an example, would be expected to promote an increase in the mobilization and utilization of carbohydrates (CHO) (8). In addition, if blood flow is compromised, O2 availability to the mitochondria may be threatened. Under such conditions, CHO oxidation becomes more emphasized, ostensibly because it provides the highest ATP yield per mole of O2 (1). An increase in blood glucose utilization has been reported to occur during submaximal exercise in hypoxia, even though oxidative phosphorylation is not compromised (2).
In this study, we have hypothesized that hypohydration resulting in a reduction in PV would alter glucose kinetics, promoting an increase in both glucose release from the liver and glucose oxidation by the working muscle. These changes would be accompanied by a decline in both the mobilization and utilization of blood free fatty acids (FFA).
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Participants.
Ten healthy young males were recruited and screened to ensure that they
were healthy and not active on a regular basis. Their mean (±SE) age,
weight, peak aerobic power (O2 peak), and maximal heart rate were 20.3 ± 0.4 yr, 78.1 ± 3.0 kg,
3.96 ± 0.14 l/min, and 199.0 ± 2.5 beats/min, respectively.
All of the experimental procedures, risks, and benefits were explained to each subject before written consent was obtained and after approval
of the study by the Office of Human Research (University of Waterloo,
Waterloo, ON).
Design and procedures.
The basic experimental design consisted of having the participants
perform a standardized, prolonged submaximal cycling test on two
separate occasions: under control conditions (CON) and after 4 days of
diuretic administration (DIU). On each of four days before each
submaximal test, subjects consumed either a diuretic (Novotriamazide; 100 mg triamterene and 50 mg hydrochlorothiazide) or a
placebo. The exercise tests were separated by a minimum of 1 wk and
were administered in a randomized, single-blind order. All exercise
measurements were conducted at approximately the same time of day for
each subject. The exercise test, which was performed at ~61%
O2 peak, was planned for a 90-min
duration. However, because some subjects were unable to complete the 90 min and because blood sampling was a problem in some subjects, we
report only on the first 60 min of exercise. Exercise was performed in
ambient temperatures (22-24°C) and humidities (35-45%).
Each participant consumed a standardized snack 4 h before each
exercise test (Ensure liquid, 1,045 kJ: 14.8% protein, 31.5% fat, and
53.7% carbohydrate; Ross Laboratories, Montreal, QC, Canada). Only
water (ad libitum) was allowed between consumption of the snack and arrival at the laboratory. All participants were instructed not to
engage in any vigorous physical activity for the duration of the
experiment and to follow a normal balanced diet.
O2 uptake measurements.
The submaximal exercise bouts were performed on an electrically braked
cycle ergometer (Quinton 870, Excalibur Sport, Groningen, Netherlands). Each of the participants had performed
progressive exercise until fatigue for measurement of
O2 peak ~1 wk before the first
submaximal test by means of a protocol that has been previously
described (16). Gas exchange and ventilatory measures were
determined using an open-circuit gas collection system
(23). The gas analyzers (Beckman OM-11 and LB-2) and the
pneumotachograph (Hewlett-Packard 4730A) were calibrated on each
testing day. Common reference gases, with the gas percentages precisely
determined, were used for the calibration. The pneumotachograph was
calibrated by using a 3-liter syringe emptied to produce a flow rate
similar to that found in exercise. For the submaximal cycling tests,
the same absolute power output (170 ± 6.7 W) was used for the two
conditions. Measurements of respiratory gas exchanges during steady
state were made over a 3- to 4-min collection period before and
intermittently during each test (0, 15, 30, and 60 min). Steady state
was confirmed by comparing consecutive 20-s periods of gas exchange.
Indirect calorimetry.
Stoichiometric equations and appropriate caloric equivalents (12,
40) were used to calculate carbohydrate (CHO) and fat oxidation
rates during the exercise. We assumed that the nitrogen excretion rate
was 135 µg · kg1 · min
1
(34). Although indirect calorimetry technically provides
for an estimation of total glucose oxidation, we have followed the general practice of labeling it as CHO oxidation.
Blood sampling.
Arterialized blood samples were collected before and at regular
intervals during exercise (0, 15, 30, 45, and 60 min). The samples were
used for the determination of blood lactate, glucose, glycerol, serum
FFA, insulin, and glucagon concentrations and for plasma glucose and
glycerol isotopic enrichment. For determination of blood metabolites
(lactate, glucose, and glycerol), whole blood was deproteinized using
ice-cold perchloric acid. After centrifugation for removal of the
precipitated proteins, ice-cold KHCO3 was added to
neutralize the samples. For analysis of serum FFA, ~1.5 ml of blood
were allowed to clot, the sample was then centrifuged, and the
resulting serum was stored until analysis. Blood samples for the
determination of glucose and glycerol enrichment were added to
heparinized tubes, the tubes were then centrifuged, and the resulting
plasma was stored for later analysis. All samples were stored at
80°C before analysis. Blood concentrations of lactate, glucose,
glycerol, and serum FFA were determined by fluorometric methods as
described previously (17). Standard radioimmunoassay methods were used to determine the serum concentration of insulin and
glucagon (Coat-A-Count, Diagnostic Products, Intermedico, Toronto, ON, Canada).
Isotopes.
The stable isotope tracers used for determination of substrate
turnover, [6,6-2H2]glucose and
[2H5]glycerol (98% enriched; MassTrace,
Woburn, MA), were diluted in sterile 0.9% saline under aseptic
conditions and then filtered through a 0.2-µm filter (Pall Gelman
Sciences, Ann Arbor, MI). Immediately before infusion, the infusate was
passed through another 0.2-µm filter (Pall Gelman Sciences). A
priming dose of glucose (14 µmol/kg) and glycerol (1.3 µmol/kg) was
administered before the initiation of a constant infusion (0.22 ± 0.03 µmol · kg1 · min
1
for [6,6-2H2]glucose and 0.1 ± 0.03 µmol · kg
1 · min
1 for
[2H5]glycerol). The specific infusion rates
for each tracer were calculated by multiplying the infusate
concentration (determined fluorometrically) by the infusion rate. The
infusion rate was doubled (as compared with rest) for both tracers at
the onset of exercise. To avoid biasing the data, the specific infusion rates and infusates were kept constant for each subject over each condition.
Tracer enrichment. Glucose and glycerol enrichments were determined using the pentaacetate derivative of glucose and the trimethylsilyl derivative of glycerol. For glucose, 250 µl of plasma were deproteinized with barium hydroxide (0.3 N) and zinc sulfate (0.3 N). The resulting supernatant was then deionized by passing it over a mixed-bed anion-cation exchange chromatographic column (AG-1-X8 and AG 50W-X8; Sigma Chemical, St. Louis, MO). The eluted fluid from this column was then lyophilized to dryness. To the lyophilized extract 100 µl of a 2:1 solution of acetic anhydride and pyridine were added to create the final derivative. Samples were then incubated at 80°C for 15 min. For glycerol, 1,000 µl of plasma were deproteinized with barium hydroxide (0.3 N) and zinc sulfate (0.3 N). The resulting supernatant was then deionized by passing it over a mixed-bed anion-cation exchange chromatographic column (AG-1-X8 and AG 50W-X8; Sigma). The eluted fluid from this column was then lyophilized to dryness. To the dry extract, 100 µl of 2:1 N,O-bis(trimethylsilyl)trifluroacetamide-pyridine were added. Extracts were then incubated at 80°C for 30 min.
Gas chromatography-mass spectrometry. Enrichment of each of the derivatives was measured by injection of 1 µl of extract into a Hewlett-Packard 6890 gas chromatography (GC) oven (Fullerton, CA). An HP-5 fused silica capillary column (15 m × 0.32 µm, 0.25-µm film thickness) was used in the GC oven (Hewlett-Packard). Mass analysis was performed using a Hewlett-Packard 5973 mass spectrometer operating in EI+ mode. Data were processed using HP-Chemstation software (Hewlett-Packard).
Selected ion masses were monitored, depending on which derivative was injected. Mass-to-charge ratios (m/z) were determined for 200, 202, 205, and 208 atomic mass units for determination of glucose and glycerol enrichment, respectively. These enrichments gave the expected M + 2/M + 0 or M + 3/M + 0 ratios, indicating that there were no other interfering products or masses. All masses were also corrected according to a linear peak area standard curve for glucose and glycerol.Calculations. The rates of appearance (Ra) and disappearance (Rd) of glucose and glycerol were calculated using the steady-state tracer dilution equation at rest (31). During exercise, isotope kinetics were calculated with the Steele equation as modified for stable isotopes, because the amount of tracer infused was no longer negligible (40).
The effective volumes of distribution were assumed to be 230 ml/kg for glycerol and 100 ml/kg for glucose. We had previously observed such volumes of distribution to be adequate under a variety of conditions (30-32). Increasing (+50%) or decreasing (Statistics. Data were analyzed using a two-way repeated-measures ANOVA for experimental condition (CON, DIU) and time (0-60 min). When a significant interaction was found (P < 0.05), the Newman-Keuls post hoc technique was used to determine pairwise differences. A paired t-test was used to analyze area under the curve data for glycerol Ra.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Respiratory gases.
Hypohydration had no effect on changes in
O2 and carbon dioxide production
(
CO2) observed during
prolonged exercise (Table 1). Exercise
led to an increase in both
O2 and
CO2 compared with rest. During exercise,
O2 was higher at 90 min than at 15 min.
The respiratory exchange ratio also significantly increased as a result
of the exercise; however, DIU had no effect. The loss of PV resulted in
an increase in hemoglobin (g/100 ml) from 15.6 ± 0.6 to 17.5 ± 0.6.
|
Blood metabolite concentration and turnover.
Arterialized venous blood lactate concentrations were increased at 15 min of exercise (Fig. 1). No further
changes were observed as the exercise progressed; in addition, no
differences were observed for DIU compared with CON. Serum FFA
decreased during the early phase of exercise but returned to resting
levels by 60 min (Fig. 2). As with plasma
lactate, DIU had no effect on serum FFA response to exercise compared
with CON.
|
|
|
|
|
|
Substrate oxidation.
Hypohydration had no effect on whole body CHO or fat oxidation during
exercise (Table 3). With the onset of
exercise, whole body CHO oxidation increased. Whole body fat oxidation
also increased during exercise but only at 60 min. Blood glucose
oxidation was different between the two experimental conditions (Table
3). DIU resulted in lower blood glucose oxidation at 15 and 30 min of
exercise, but by 60 min of exercise, blood glucose oxidation was not
different between DIU and CON. Exercise also led to a progressive
increase in blood glucose oxidation in both conditions. Calculated
muscle glycogen oxidation was not different between the two conditions
(Table 3). In general, exercise led to a decline in muscle glycogen
oxidation at 60 min (Table 3).
|
Hormones.
In both conditions, exercise resulted in an increase and a decrease in
plasma glucagon and insulin, respectively (Table
4). For plasma glucagon, the
concentration was greater by the end of exercise (60 min) compared with
rest. In contrast, exercise led to a rapid decline in plasma insulin
that was evident by 30 min of exercise. No further reduction was
observed after 30 min. DIU had no effect on plasma insulin
concentration; for plasma glucagon, however, the concentration with DIU
was greater than in CON.
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
As hypothesized, the diuretic-induced reductions in PV altered the
glucoregulatory response to prolonged moderate-intensity exercise. Both
plasma glucose Ra and Rd and the rate of
glucose oxidation were depressed early in exercise with DIU compared
with CON, which was unexpected. However, by 60 min of exercise, these changes were either reversed (Ra) or not statistically
different (glucose oxidation). Interestingly, the alterations in blood
glucose regulation and metabolism were not accompanied by changes in
fat oxidation, whole body lipolysis, and total CHO oxidation. In
addition, although no differences were observed for plasma insulin
concentration between the two conditions, plasma glucagon was elevated
after the reduction in PV. The sympathetic drive also appeared to be increased after DIU, as indicated by the progressive difference in NE
concentration that was observed during exercise (35). No
differences were found between the two conditions in the EPI response
(35). It should be emphasized that, even though the exercise was conducted at the same absolute intensity before and after
hypohydration, the relative work load might increase if the PV loss
induced a decrease in O2 peak. At least
for diuretic-induced reductions in PV, however, this does not appear to
occur (36).
In the current study, we used a model of diuretic administration to
induce a reduction in plasma volume. The 4 days of Novotriamazide administration (100 mg triamterene and 50 mg hydrochlorothiazide) led
to an ~14.6% decline in resting PV. Hydrochlorothiazide is a
moderately potent diuretic that acts on the early distal convoluted tubule, whereas triamterene is a mildly potent diuretic that acts on
the late distal convoluted tubule (33). Triamterene is
considered a potassium-sparing diuretic that, when used in combination
with diuretics like hydrochlorothiazide, prevents the kaluresis that is
normally associated with its (hydrochlorothiazide) use
(33). In addition, there is evidence to suggest that the
combination of these drugs, taken over both the long term and the short
term, have little influence on serum Na+, K+,
Cl, Mg2+, Ca2+, urate,
creatinine, and blood glucose concentrations (25). We have
previously used similar doses of hydrochlorothiazide and triamterene
that resulted in similar PV losses (41). In the current
and the previous studies (41), the diuretic induced an
isoosmotic hypovolemia. Diuretics act primarily to decrease extracellular fluid volume, both plasma volume and interstitial volume.
Other models used to induce hypohydration, such as heat dehydration,
exercise, and heat and fluid restriction, all result in an elevation in
osmolality (36). With these forms of hypohydration, the
hyperosmolality mobilizes fluid from the intracellular to the
extracellular space in an attempt to defend against the PV loss
(36). As a consequence, the manner in which the reduction in PV is induced may result in different physiological responses during
exercise. It is acknowledged that the possibility exists that the
effects that we have observed on glucose Ra and
Rd may not be due to the hypohydration but could be a
direct effect of the diuretic itself.
Hypohydration altered the hormonal response to exercise in a manner opposite to what is normally observed with endurance training. With training, there is a significant reduction in the sympathoadrenal drive, as indicated by the reduction in NE concentration, which is most dramatic late in exercise (3). Unlike in the DIU model, there is also a large reduction in the blood Epi response (3). In addition, plasma glucagon is decreased and not increased, as was observed during exercise after DIU (3). Despite these differences, glucose Ra was significantly lower at rest and at 15 and 30 min of exercise. This suggests that the elevated levels of glucagon did not influence glucose Ra, despite suggestions that glucagon is one of the major regulators of hepatic glucose production (24, 39). It appears that the elevated plasma glucose concentration occurred as a result of a decline in the uptake of plasma glucose by the various tissues in the body. Support for this possibility is found with the glucose Rd data, which demonstrate that glucose Rd with DIU was attenuated both at rest and early in the exercise (15 and 30 min) compared with CON. It is also possible that the elevated blood glucose level was also involved in inhibiting hepatic glucose output, as has been previously observed when blood glucose levels are elevated (20). Gonzalez-Alonso et al. (13) also observed that exercise-induced dehydration leads to similar alterations in blood glucose concentrations late during prolonged exercise (13). They reported greater increases in the concentration of plasma glucagon with dehydration. Therefore, it appears that diuretic-induced alterations in PV and dehydration both have an impact on blood glucose regulation. However, it should be noted that, in the current study, all measures of blood metabolites and hormones were taken from a peripheral vein and may not reflect concentrations in the portal vein. Finally, other factors have also been implicated in the control of endogenous glucose production (39), and further work is required to determine the mechanisms that are involved in the observed changes.
Generally, the onset of exercise leads to a very rapid and large increase in glucose Ra, which then continues to increase at a much more moderate and linear rate of increase as the exercise progresses (3, 24). In the present study, CON demonstrated a linear glucose Ra response to continued dynamic exercise; however, DIU led to a curvilinear increase in glucose Ra as the exercise progressed. The uptake of glucose as estimated by glucose Rd followed a similar pattern to what was observed with endogenous glucose production. It appears that, early in exercise, DIU led to a decreased reliance on endogenous glucose, but as exercise continued, there was an almost exponential increase in endogenous glucose production and in glucose uptake. These changes do not appear to be related to alterations in plasma glucose, insulin, and glucagon concentrations. Despite the main effects for both plasma glucagon and glucose, the relative changes with the exercise were similar for both experimental conditions. Therefore, if the alterations in glucose regulation had been due to changes in either plasma glucose or glucagon, a differential response between these variables would have been expected during exercise between CON and DIU.
The alterations in glucose Ra and Rd in the current study may have been related to the differences in thermoregulation that were also observed (35). The DIU condition resulted in a greater and more rapid rise in core temperature. It has been previously observed that heat stress significantly alters endogenous glucose production during exercise (21). Specifically, exercise in a higher ambient temperature increased glucose Ra and respiratory exchange ratio (RER), indicating an increased rate of carbohydrate oxidation (21). That increase in glucose Ra and RER was associated with an increase in plasma glucagon that was also observed late in exercise with the added heat stress (21). As part of the same study, an increased rate of muscle glycogenolysis was also observed, which supports the notion of a shift toward increased CHO utilization (9).
In the current study, total CHO oxidation did not differ during exercise in DIU compared with CON. Similarly, there was no difference in muscle glycogen oxidation between conditions. In contrast, plasma glucose oxidation, particularly early in exercise, was decreased. Because glucose oxidation represents <15% of the total CHO oxidation, and because the reduction in glucose oxidation was small with DIU, the impact on total CHO oxidation was minimal. With our protocol, fat oxidation represents only a small percentage of the total substrate oxidized. As expected, time-dependent increases in fat oxidation occurred during the exercise. Although not significant (P = 0.06), there was a strong trend for fat oxidation to become more pronounced later in the exercise with DIU. A similar effect was also indicated for glucose oxidation. Unfortunately, due to fatigue the exercise could not be sustained for a longer period of time. Although it is tempting to suggest that differences in substrate utilization between conditions might have become more emphasized if the exercise could have been prolonged beyond 60 min, we do not know what would happen.
Abnormal elevations in muscle temperature, which would also be expected to occur with DIU given the increase in core temperature that was observed (35), have been demonstrated to alter muscle metabolism and substrate oxidation (7, 9, 10, 21). Work in the heat, which resulted in elevations in muscle temperature, led to increased rates of muscle glycogenolysis and a decreased reliance on extramuscular substrates (9, 21, 22). Our results appear to be consistent with the decreased reliance on blood substrates, at least for glucose. Interestingly, the fact that we did not find any differences in blood Epi concentrations during exercise between the two conditions suggests that other factors are involved in mediating the increase in glycogenolysis previously observed (9). Increased Epi levels were shown previously to enhance muscle glycogenolysis during exercise (8).
The reduction in PV induced by DIU did not have an effect on glycerol Ra or whole body lipolysis during exercise but did lead to elevated concentrations of plasma glycerol both at rest and during exercise. The trend toward an increase in lipolysis with DIU was not significant. It is noteworthy that rest values for both blood glycerol and lipolysis appear to account for any change observed during exercise between conditions. Because plasma NE was not elevated during this period after PV loss, the elevated glucagon levels appear to be involved. Plasma NE levels were greatly exaggerated late in the exercise (35). However, no changes in either lipolysis or utilization were observed at this time. These observations appear to challenge the role of NE in fat turnover (27). On the other hand, it is possible that measurements of plasma NE concentration have limited significance, given that NE control of lipolysis is based on local release from adipose tissue (39). Collectively, it appears that the reduction in plasma volume may influence lipolysis, possibly through an alteration in the endocrine response to exercise. The increases in blood glycerol concentration with DIU were unexpected, since no changes were observed in glycerol Ra. With the reductions in cardiac output discussed earlier, it is possible that splanchnic blood flow could have been reduced with DIU. A reduction in flow could result in a decline in glycerol clearance, as the liver is the primary site of glycerol uptake (4, 26).
In summary, we observed that reductions in PV mediated by diuretic administration altered glucose kinetics during prolonged exercise of moderate intensity. The specific effect depended on the time of exercise. Early in exercise, plasma glucose release from the liver and utilization by muscle decreased, whereas late in exercise these effects were reversed. These changes occurred in the absence of changes in whole body lipolysis and fat oxidation. Hypohydration would appear to be an important factor in understanding the changes in control of substrate turnover and oxidation that occur with exercise and training.
![]() |
ACKNOWLEDGEMENTS |
---|
The authors would like to thank L. Giangregorio and K. Parks for their technical assistance during the data collection of this study.
![]() |
FOOTNOTES |
---|
This study was supported by the Natural Sciences and Engineering Research Council of Canada.
Address for reprint requests and other correspondence: H. J. Green, Dept. of Kinesiology, Univ. of Waterloo, Waterloo, ON, Canada N2L 3G1 (E-mail: green{at}healthy.uwaterloo.ca).
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. Section 1734 solely to indicate this fact.
Received 10 March 2000; accepted in final form 11 August 2000.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Astrand, PO,
and
Rodahl K.
Textbook of Work Physiology. New York, NY: McGraw Hill, 1986, p. 523-576.
2.
Brooks, GA,
Butterfield GE,
Wolfe RR,
Groves BM,
Mazzeo RS,
Sutton JR,
Wolfel EE,
and
Reeves JT.
Increased dependence on blood glucose after acclimatization to 4,300 m.
J Appl Physiol
70:
919-927,
1991
3.
Coggan, AR,
and
Williams BD.
Metabolic adaptations to endurance training: substrate metabolism during exercise.
In: Exercise Metabolism, edited by Hargreaves M.. Champaign, IL: Human Kinetics, 1995, p. 177-210.
4.
Coppack, SW,
Jensen MD,
and
Miles JM.
In vivo regulation of lipolysis in humans.
J Lipid Res
35:
177-193,
1994[Abstract].
5.
Coyle, EF,
and
Hamilton M.
Fluid replacement during exercise. In: Perspectives in Exercise Science and Sports Medicine, Vol. 3. Fluid Homeostasis During Exercise, edited by Gilsolfi CV,
and Lamb DR.. Carmel, IN: Benchmark, 1990, p. 281-308.
6.
Fallo, F.
Renin-angiotensin-aldosterone system and physical exercise.
J Sports Med Phys Fitness
33:
306-312,
1993[ISI][Medline].
7.
Febbraio, MA,
Carey MF,
Snow RJ,
Stathis CG,
and
Hargreaves M.
Influence of elevated muscle temperature on metabolism during intense, dynamic exercise.
Am J Physiol Regulatory Integrative Comp Physiol
271:
R1251-R1255,
1996
8.
Febbraio, MA,
Lambert DL,
Starkie RL,
Proietto J,
and
Hargreaves M.
Effect of epinephrine on muscle glycogenolysis during exercise in trained men.
J Appl Physiol
84:
465-470,
1998
9.
Febbraio, MA,
Snow RJ,
Stathis CG,
Hargreaves M,
and
Carey MF.
Effect of heat stress on muscle energy metabolism during exercise.
J Appl Physiol
77:
2827-2831,
1994
10.
Febbraio, MA,
Snow RJ,
Stathis CG,
Hargreaves M,
and
Carey MF.
Blunting the rise in body temerature reduces muscle glycogenolysis during exercise in humans.
Exp Physiol
81:
685-693,
1996[Abstract].
11.
Fortney, SM,
Wenger CB,
Bove JR,
and
Nadel ER.
Effects of hyperosmolality on control of blood flow and sweating.
J Appl Physiol
57:
1688-1695,
1984
12.
Frayn, KN.
Calculation of substrate oxidation rates in vivo from gaseous exchange.
J Appl Physiol
55:
628-634,
1983
13.
Gonzalez-Alonso, J,
Calbet JAL,
and
Nielsen B.
Metabolic and thermodynamic responses to dehydration-induced reductions in muscle blood flow in exercising humans.
J Physiol (Lond)
520:
577-589,
1999
14.
Gonzalez-Alonso, J,
Mora-Rodriguez R,
Below PR,
and
Coyle EF.
Dehydration markedly impairs cardiovascular function in hyperthermic endurance athletes during exercise.
J Appl Physiol
82:
1229-1236,
1997
15.
González-Alonso, J,
Mora-Rodriguez R,
Below PR,
and
Coyle EF.
Dehydration reduces cardiac output and increases systemic and cutaneous vascular resistance during exercise.
J Appl Physiol
79:
1487-1496,
1995
16.
Green, HJ,
Jones LL,
Hughson RL,
Painter DC,
and
Farrance BW.
Training-induced hypervolemia: lack of an effect on oxygen utilization during exercise.
Med Sci Sports Exerc
19:
202-206,
1987[ISI][Medline].
17.
Green, HJ,
Jones S,
Ball-Burnett M,
and
Fraser I.
Early adaptations in blood substrates, metabolites, and hormones to prolonged exercise training in man.
Can J Physiol Pharmacol
69:
1222-1229,
1991[ISI][Medline].
18.
Grieve, DA.
The ergo reflex in patients with chronic stable heart failure.
Int J Cardiol
68:
157-164,
1999[ISI][Medline].
19.
Guyton, AC,
and
Hall JE.
Textbook of Medical Physiology. Toronto, Canada: Saunders, 1996.
20.
Hargreaves, M.
Skeletal muscle carbohydrate metabolism during exercise.
In: Exercise Metabolism, edited by Hargreaves M.. Champaign, IL: Human Kinetics, 1995, p. 41-72.
21.
Hargreaves, M,
Angus D,
Howlett K,
Marmy-Cenus N,
and
Febbraio M.
Effect of heat stress on glucose kinetics during exercise.
J Appl Physiol
81:
1594-1597,
1996
22.
Hargreaves, M,
Dillo P,
Angus D,
and
Febbraio M.
Effects of fluid ingestion on muscle metabolism during prolonged exercise.
J Appl Physiol
80:
363-366,
1996
23.
Hughson, RL,
Kowalchuk JM,
Prime WM,
and
Green HJ.
Open-circuit gas exchange analysis in the non-steady state.
Can J Appl Sport Sci
5:
15-18,
1980[Medline].
24.
Kjaer, M.
Hepatic fuel metabolism during exercise.
In: Exercise Metabolism, edited by Hargreaves M.. Champaign, IL: Human Kinetics, 1995, p. 73-97.
25.
Kohuakka, A,
Salo H,
Gordin A,
and
Eisalo A.
Antihypertensive and biochemical effects of different doses of hydrochlorothiazide or in combination with traimterine.
Acta Med Scand
219:
381-386,
1986[ISI][Medline].
26.
Larsen, JA.
Elimination of glycerol as a measure of hepatic blood flow in the cat.
Acta Physiol Scand
57:
224-234,
1963[ISI].
27.
Martin, WH, III.
Effects of acute and chronic exercise on fat metabolism.
In: Exercise and Sport Science Reviews, edited by Holloszy JO.. Baltimore, MD: Williams and Wilkins, 1996, vol. 24, p. 203-231.
28.
Newsholme, EA,
and
Taylor K.
Glycerol kinase activities in muscles from vertebrates and invertebrates.
Biochem J
112:
465-474,
1969[ISI][Medline].
29.
Pawelczyk, JA,
Hanel B,
Pawelczyk RA,
Warberg J,
and
Secher NH.
Leg vasoconstriction during dynamic exercise with reduced cardiac output.
J Appl Physiol
73:
1838-1846,
1992
30.
Phillips, SM,
Green HJ,
Grant SM,
MacDonald MJ,
Sutton JR,
Hill RE,
and
Tarnopolsky MA.
The effects of acute volume expansion on substrate turnover during prolonged low-intensity exercise.
Am J Physiol Endocrinol Metab
273:
E297-E304,
1997
31.
Phillips, SM,
Green HJ,
Tarnopolsky LJ,
Heigenhauser GM,
Hill RE,
and
Grant SM.
Effects of training on substrate turnover and oxidation during exercise.
J Appl Physiol
81:
2182-2191,
1996
32.
Phillips, SM,
Green HJ,
Tarnopolsky MA,
and
Grant SM.
Decreased glucose turnover following short term training.
Med Sci Sports Exerc
26:
S34,
1994.
33.
Puschett, JB.
Pharmacological classification and renal actions of diuretics.
Cardiology
84:
4-13,
1994[ISI][Medline].
34.
Romijn, JA,
Coyle EF,
Sidossis LS,
Gastaldelli A,
Horowitz JF,
Endert E,
and
Wolfe RR.
Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration.
Am J Physiol Endocrinol Metab
265:
E380-E391,
1993
35.
Roy, BD,
Green HJ,
and
Burnett M.
Prolonged exercise following diuretic-induced hypohydration. Effects on cardiovascular and thermal strain.
Can J Physiol Pharmacol
78:
541-547,
2000[ISI][Medline].
36.
Sawka, MN,
and
Coyle EF.
Influence of body water and blood volume on thermoregulation and exercise in the heat.
In: Exercise and Sport Science Reviews, edited by Holloszy JO.. New York: Lippincott, Williams and Wilkins, 1999, p. 167-218.
37.
Van Beaumont, W,
Greenleaf JE,
and
Juhos L.
Disproportional changes in hematocrit, plasma volume, and proteins during exercise and bed rest.
J Appl Physiol
33:
55-61,
1972
38.
Wade, CE,
and
Freund BJ.
Hormonal control of blood volume during and following exercise.
In: Perspectives in Exercise, Science and Sports Medicine: Fluid Homeostasis During Exercise, edited by Gisolfi CV,
and Lamb DR.. Carmel, IN: Cooper, 1990, p. 207-245.
39.
Wasserman, DH,
and
Cherrington AD.
Regulation of extramuscular fuel sources during exercise.
In: Handbook of Physiology. Exercise, Regulation and Integration of Multiple Systems. Bethesda, MD: Am. Physiol. Soc, 1996, sect. 12, chapt. 23, p. 1036-1074.
40.
Wolfe, RR.
Radioactive and Stable Isotope Tracers in Biomedicine. New York: Wiley-Liss, 1992, p. 119-164.
41.
Zappe, DH,
Helyar RG,
and
Green H.
The interaction between short-term training and a diuretic induced hypovolemic stimulus.
Eur J Appl Physiol
72:
335-340,
1996.
HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Visit Other APS Journals Online |