Acute altitude exposure has profound affects on body fluid balance, and the magnitude of perturbation is probably dependent upon both the altitude and duration of exposure (25). The effect of hypoxia on hormones involved in the regulation of body fluid balance has been extensively studied. At rest, acute exposure to hypoxia for 90 min has no effect on the plasma concentration of the atrial natriuretic factor ([ANF]) (26), whereas it induces an increase after 120 min (6,8). Plasma levels of arginine vasopressin ([AVP]) and renin activity (ARP) do not increase until 120 min of exposure to hypoxia (6,8). The specific sensitivity of the hormonal system to hypoxia clearly appears to be influenced by the time of exposure, because after 48 h of hypoxia, it has been shown that ARP and plasma concentration of aldosterone ([Aldo]) are no longer increased but on the contrary are decreased compared to values at sea level (21).
Results obtained during exercise are more conflicting than at rest. It has been shown that ARP increased during exercise in a hypoxic environment (3,4,19,20) or decreased (17,18), or had the same time course as in normoxia but with lower values (21). Although a dissociation between ARP and [Aldo] has been shown in response to hypoxia in some studies (3,4,20), others had described a similar increase in ARP and [Aldo] (21). [AVP] either did not change during mild exercise performed in hypoxia compared with rest and sea level values (18) or had the same exercise-induced increase in hypoxia and normoxia in healthy subjects (1). Studies evaluating the response of ANF had shown either that hypoxia did not have an affect [ANF] during mild exercise or that the exercise-induced increase in [ANF] was blunted under hypoxic conditions (21,26). Discrepancies between these results may be explained by the different levels of altitude achieved, different durations of exposure at a given altitude, and different hydration levels of the subjects. Moreover, accurate quantification of water losses was poorly described in these studies. Furthermore, the characteristics of exercise (intensity, duration and type of exercise) performed either in field or laboratory conditions appear to be very different from one study to another.
Acute exposure to high altitude leads to significant decrements in maximal oxygen uptake (V̇O2max) compared with sea level (9,16). As a consequence, the relative intensity or fraction V̇O2max at a given absolute workload increases in hypoxic conditions. Many physiological responses have been reported to be dependent on the relative intensity of exercise rather than the absolute workload. To our knowledge, no study has considered the time course of hormonal changes in hypoxia during exercise performed both at the same relative and the same absolute intensities.
The present experiment was therefore designed to describe the effects of acute hypobaric hypoxia on fluid-regulatory hormones during exercise. We hypothesized that the levels of AVP, Aldo, ARP, and ANF would be dependent on the relative intensity of exercise and then would be higher in hypoxia than in normoxia at the same absolute workload. We measured these hormones over time as well as the variations in plasma volume and plasma osmolality during 60 min of cycling exercise performed either in hypoxia or in normoxia at the same absolute and the same relative intensity.
METHODS
Subjects.
Thirteen male volunteers gave their written informed consent to participate in the experiment after the details of the protocol had been explained to them. Women were excluded from the experiment because it has been recently shown that substrate oxidation in women is altered differently from men during exercise upon acute altitude exposure (2). This may have consequences on the body fluid balance, considering that glycogen breakdown and substrate oxidation are potential sources of endogenous water. This study was approved by the Committee on Human Protection in Biomedical Research in Grenoble, France. The selection of the subjects was based on a clinical investigation comprising a detailed medical history, a physical examination and general blood screening, all normal for the subjects. All the participants trained regularly for endurance cycling and were nonacclimatized white lowlanders. Their mean ± SEM anthropomorphic characteristics were age 22.6 ± 0.7 yr, body mass 67 ± 2 kg, and height 1.76 ± 0.01 m. Their maximal oxygen uptake (V̇O2max) was determined both in normoxia (V̇O2maxN, barometric pressure, PB = 992 hPa) and in hypoxia (V̇O2maxH, PB = 594 hPa, simulated altitude 4400 m), using an altitude configured breath-by-breath automated gas exchange system (MedGraphics CPX/D, Medical Graphics, St. Paul, MN) during a graded maximal exercise test performed on a Monark cycle ergometer.
Research design.
Four experimental trials were completed: H55 and H75 for hypoxia at 55% and 75%, respectively, of hypoxia maximal aerobic power; N55 for normoxia at the same absolute metabolic rate as H75; N75 for normoxia at 75% of normoxia maximal aerobic power. For each subject, the trials were separated by at least 5 d and were performed at the same time in the morning or afternoon after a standard meal. Three days before each trial, the subjects consumed a standardized diet (sodium, 140 mmol·d−1 and potassium, 70 mmol·d−1), and they were asked to refrain from strenuous exercise and to drink at least 2 L of water daily. Their individual hydration status was evaluated upon their arrival at the laboratory by measuring the osmolality of urine sampled in the morning of the trial, and blood measurements of hematocrit, serum osmolality, and sodium concentration in the beginning of the exercise.
The trials consisted in 60 min of exercise on a Monark cycle placed in the low barometric pressure chamber (TIM, Marseille, France, volume 30 m3). The target power was reached after a 5-min warm-up at half intensity. In all trials, the temperature in the chamber remained constant (21–22°C), with relative humidity between 40 and 60%; wind velocity near the subject was 0.5–1.0 m·s−1. No rehydration was given during exercise.
On arriving at the laboratory, subjects put on shorts and probes were attached to them. During normoxia trials, they sat for 30 min at rest on the saddle of the cycle ergometer in the hypobaric chamber (PB = 992 hPa, altitude 250 m) before the exercise began. During the hypoxic trials, in addition to the experimenters, subjects were accompanied by a physician, who breathed O2 through an O2 diluter demand mask (Eros MC 10, Plaisir, France). The chamber was flushed with medical air quality gas to maintain the inspired fractions of O2 and CO2 at 21% and near 0%, respectively. The subjects wore a finger oximeter (Kontron Instruments, Watford, UK), and their arterial O2 saturation was continuously observed by a second physician outside the hypobaric chamber. A radio contact was established between the two physicians. To reach the target altitude, the pressure in the chamber was lowered at a constant rate of 5 m·s−1 up to 4400 m (PB = 594 hPa), which took about 15 min. Then the subjects remained quietly for 30 min at rest on the saddle of the cycle ergometer before the exercise began. At the end of exercise, the chamber was recompressed at the same rate (5 m·s−1).
Physiological measurements.
Before entering the hypobaric chamber, subjects emptied their bladders and were weighed (Sebag-Pesage 286, Villeurbanne, France; accuracy ± 10 g). At the end of exercise, the subjects were weighed again and urine was collected. The volume of urine collected after exercise was immediately measured.
Throughout the experimental session, the heart rate (HR) was recorded every min with a telemetry system (Polar Sport Tester XtrainerPlus, Polar Electro Oy, Kempele, Finland) and rectal (Tre) and four cutaneous temperatures were recorded every min with thermistances (YSI series 400, Yellow Springs, OH). Mean skin temperature (T̄sk) was calculated using the equation of Ramanathan (22). Oxygen uptake (V̇O2) was measured continuously by the altitude configured breath-by-breath automated gas exchange system (MedGraphics CPX/D).
Biochemical assays.
A polyethylene catheter (Angiocath F2818 Deseret) was inserted in an antecubital vein 1 h before the exercise began and linked to an extension. As soon as they sat on the saddle of the ergocycle, the subjects were asked to position their arms lying on the handlebars. At rest and during exercise, blood was sampled from the arm in that control position.
The first blood sample, used as the reference for the calculation of plasma volume changes (ΔVP), was collected after 30 min spent at rest on the saddle of the cycle ergometer before exercise; this period was necessary to stabilize hemodynamic conditions. Thereafter, venous blood samples were drawn 15, 30, 45, and 60 min after the beginning of exercise.
Blood samples were transferred into tubes containing 1) ethylene diamine tetra-acetic acid (EDTA) for measurements of hematocrit (Hct) and concentration of hemoglobin ([Hb]); 2) EDTA and 20 μL of aprotinin for measurement of plasma renin activity (ARP) and aldosterone ([Aldo]); 3) lithium-heparin for measurement of plasma osmolality (Posm); and 4) lithium-heparin and 20 μL of aprotinin for measurement of plasma concentrations of arginine vasopressin ([AVP]), atrial natriuretic factor ([ANF]), and noradrenaline ([NA]).
Blood samples were analyzed in quadruplicate for Hct using microcentrifugation and in duplicate for [Hb] using an automated hematological cell counter (T 890, Coulter Systems, Paris, France). All other tubes were centrifuged (10 min, 3000 RPM, +4°C) to take samples of plasma. Posm was immediately measured by freezing point depression (AUTOCAL 13/13 DR Osmometer, Roebling Messtechnik, Berlin, Germany); the remaining plasma was stored at −80°C until required for further assay.
ARP and [Aldo] were assayed by radioimmunoassay using commercial kits (Renin III generation and Aldosterone RIA, ERIA Pasteur, Marnes la Coquette, France). The sensitivity of the renin assay was 1 pg·mL−1; the intra- and interassay variabilities were 4.0 and 7.4%, respectively, and the recovery of renin was 105%. For [Aldo], the sensitivity was 10 pg·mL−1; the recovery was 90% and the intra- and interassay variabilities were 7.7 and 8.9%, respectively. [AVP] was assayed by radioimmunoassay using the method of Skowsky et al. (27). The sensitivity for AVP assay was 0.3 pg·mL−1. The intra- and interassay coefficients of variation were 3 and 11%, respectively, and the recovery of AVP was 75%. [ANF] was assayed by radioimmunoassay after extraction using Sep-Pack cartridges (10). The sensitivity for [ANF] was 1.5 pg·mL−1, and the intra- and interassay coefficients of variation were 10 and 12%, respectively. [NA] was measured using high-performance liquid chromatography with electrochemical detection (23). All within subject samples were analyzed in the same kit.
Calculations.
Total sweat loss was estimated from the difference in nude body mass before and after the exercise, adjusted for metabolic respiratory mass loss and water respiratory loss according to Houdas and Colin (14). ΔPV was calculated from changes in Hct and [Hb] according to the equation of Dill and Costill (7). Greenleaf et al. (13) have suggested that the Hct and [Hb] equations can be used during short-term (≤2 h) periods of stress if changes in plasma osmolality are less than 13 mosmol·kg−1H2O.
Statistical analysis.
A two-way ANOVA for repeated measures was conducted for time-course measured variables; a one-way ANOVA for repeated measures was conducted for body mass loss. When an overall difference was found for experimental conditions (N55, N75, H55, H75) or time, a Tukey post hoc test was used to examine significant differences among means. The null hypothesis was rejected when P < 0.05. Results are presented as means ± SEM.
RESULTS
Oxygen uptake and arterial O2 saturation.
Values of V̇O2maxH and V̇O2maxN were 3317 ± 94 and 4582 ± 129 mL·min−1, respectively, which means that V̇O2maxH corresponded to 73 ± 2% of V̇O2maxN; the mean decline in V̇O2max induced by hypoxia was 27 ± 2%.
During exercise in normoxia at the highest intensity [215 ± 8 W], V̇O2 reached on an average 3379 ± 107 mL·min−1, which corresponded to 74% of V̇O2maxN. H75 and N55 were performed at 151 ± 6 W. Mean V̇O2 was 2460 ± 66 and 2431 ± 71 mL·min−1 for H75 and N55, respectively, which corresponded to 74% V̇O2maxH during H75, and 53% V̇O2maxN during N55. H55 was performed at 95 ± 7 W, and mean V̇O2 reached 1759 ± 62 mL·min−1.
Arterial O2 saturation did not change during normoxic trials (96.4 ± 1.2% and 97.7 ± 0.7% at the beginning of exercise, 96.8 ± 0.7% and 95.7 ± 0.9% at the end of exercise, for N55 and N75, respectively). Arterial O2 saturation was lower at the beginning of exercise in hypoxia than in normoxia (83.4 ± 2.0 and 84.1 ± 4.4%, for H75 and H55, respectively) and did not change during H55 (82.3 ± 3.3% at the end of exercise), whereas it slightly decreased during H75 (76.2 ± 3.0% at the end of exercise).
Heart rate.
HR was similar during the first 25 min of exercise of N75 and H75. During the second half of exercise, HR remained stable during H75, whereas a drift was observed during N75. During N55, HR was lower than during N75 and H75 (P < 0.05), and no drift was observed. During H55, HR was lower than during N75 and H75, and only slightly higher than during N55 (P < 0.05).
Water losses.
The total water loss during exercise was 30% higher during N75 than during N55 (1008 ± 36 mL and 742 ± 50 mL, respectively, P < 0.05). The amount of total water loss was intermediate during H75 (853 ± 50 mL) compared with N75 and N55. The total water loss was the lowest during H55 (600 ± 90 mL). Water loss through respiration was higher during N75 (121 ± 4 mL, P < 0.05) than during N55, H75, and H55. During H75, it was 16% lower than during N55 (74 ± 3 mL and 88 ± 3 mL respectively, P < 0.05). Respiratory water loss was the lowest during H55 (46 ± 2 mL, P < 0.05 compared with H75 and N55).
The amount of sweat lost was higher during N75 (804 ± 36 mL, P < 0.05) than during N55 and H75 (492 ± 31 mL and 617 ± 37 mL, respectively; P < 0.05); it was higher during H75 than during N55 (P < 0.05). Sweat loss was the lowest during H55 (308 ± 19 mL; P < 0.05 compared with H75 and N55).
Although urinary water loss was the lowest during N75, there was no statistical difference in the quantity of urine produced during exercise among the trials (84 ± 19, 161 ± 33, 163 ± 32, and 245 ± 111 mL for N75, N55, H75, and H55, respectively).
ΔPV and Posm.
The similar Hct values at rest (38.86 ± 0.49, 38.72 ± 0.69, 38.66 ± 0.32, and 38.72 ± 0.43% for N55, N75, H55, and H75, respectively) and [Hb] (13.89 ± 0.21, 14.05 ± 0.20, 14.01 ± 0.13, 13.78 ± 0.21 g·L−1 for N55, N75, H55, and H75, respectively) indicate that absolute plasma volume did not differ at the beginning of each protocol.
For the four trials, plasma volume (PV) decreased in the first 15 min of exercise and then remained stable until the end of exercise (P < 0.05). Similar variations were observed during H75 and N75 (−6.8 ± 0.9% and −6.1 ± 0.9%, respectively), which were much greater than during N55 (−4.0 ± 1.0%, P < 0.05) and H55 (−2.5 ± 1.2%, P < 0.05).
Similar values of Posm were observed at rest (297.8 ± 1.4, 299.5 ± 1.4, 299.0 ± 1.0 and 297.8 ± 1.4 for N55, N75, H55, and H75, respectively). For the four trials, Posm increased in the first 15 min of exercise, with a greater initial increase during N75 than during N55 (P < 0.05). Then Posm remained stable until the end of exercise (P < 0.05), with higher values during N75, H75 and H55 (306.4 ± 1.3, 304.6 ± 2.0 and 304.4 ± 1.3 mosm·kg−1H2O, respectively) than during N55 (301.5 ± 2.0 mosm·kg−1H2O; P < 0.05).
Body temperatures.
Rectal temperature (Tre, Fig. 1A) was similar at rest whatever the protocol and increased during exercise. The rise in Tre was greater during N75 than during N55, H75, and H55 (P < 0.05). Tre was slightly higher during H75 than during H55 from the 20th minute of exercise (P < 0.05) and than during N55 during the last 15 min of exercise (P < 0.05). Tre was lower during H55 than during N55 between 15 and 45 min of exercise (P < 0.05) and then was no longer different.
;)
FIGURE 1—Time course of rectal temperature (A) and mean skin temperature (B) during N55 (□), N75 (▪), H55 (▵), and H75 (▴). Values are expressed as mean ± SEM; *: P < 0.05 compared with N55 value; Δ P < 0.05 compared with H75 value; $ P < 0.05 compared with H55 value; t/t0, P < 0.05 compared with t10 value; t/t5, P < 0.05 compared with t10 value; t/t10, P < 0.05 compared with t10 value; t/t15, P < 0.05 compared with t15 value; t/t20, P < 0.05 compared with t20 value.
At rest, mean skin temperature (T̄sk, Fig. 1B) was similar during H55, N55, and N75 and slightly higher in H75 than during N55 (P < 0.05). During the first 10 min of exercise, a decrease in T̄sk was observed during N55, N75, and H75 (P < 0.05) but not during H55; T̄sk remained higher during H75 than during normoxic trials (P < 0.05 vs N55 at t5 and t10, P < 0.05 vs N75 at t10). Between t10 and t25, T̄sk increased moderately during N55 and H75 and markedly during N75, with higher values during N75 compared with H75, H55, and N55 (P < 0.05). Then T̄sk remained stable until the end of exercise during N75, H75, and N55, with values similar during H75 and N55 and lower than during N75 (P < 0.05). During H55, T̄sk showed a slight tendency to increase between t10 and t30 and remained stable until the end of exercise, with the lowest values compared to the other trials.
Hormonal plasma levels.
Plasma levels of AVP, ANF, Aldo, ARP, and NA were similar at rest during the four protocols (Figs. 2 and 3).
FIGURE 2—Time course of plasma concentrations of arginine vasopressin ([AVP]) (A), and atrial natriuretic factor ([ANF]) (B) during N55 ((□), N75 (▪), H55 (▵), and H75 (▴). Values are expressed as mean ± SEM; *: P < 0.05 compared with N55 value; Δ P < 0.05 compared with H75 value; $ P < 0.05 compared with H55value; t/t0, P < 0.05 compared with t0 value; t/t15, P < 0.05 compared with t15 value.
FIGURE 3—Time course of plasma concentrations of aldosterone ([Aldo]) (A), plasma rennin activity (ARP) (B) and noradrenaline ([NA]) (C) during N55 □), N75 (▪), H55 (▵), and H75 (▴). Values are expressed as mean ± SEM; *: P < 0.05 compared with N55 value; Δ P < 0.05 compared with H75 value; $ P < 0.05 compared with H55value; t/t0, P < 0.05 compared with t0 value; t/t15, P < 0.05 compared with t15 value.
[AVP] was stable during N55, H55 and H75 until the 45th minute of exercise, with no differences among the trials (Fig. 2A). Thereafter, [AVP] increased markedly during N75 (P < 0.05), with values at the end of exercise higher during N75 than during N55, H75, and H55 (P < 0.05). [AVP] also increased at the end of exercise during H75 and H55, with values higher than during N55 (P < 0.05).
[ANF] increased throughout exercise, whatever the condition (Fig. 2B). This increase was greater during N75 compared to N55 and H55 (P < 0.05) and higher during H75 than during N75, N55 and H55 (P < 0.05). Then values of [ANF] were higher from the 30th minute of exercise during H75 compared with N75, N55, and H55 (P < 0.05), and during N75 compared with N55 and H55 (P < 0.05). The time course of [ANF] was similar during N55 and H55.
[Aldo] increased slightly with similar values during N55, H55, and H75 during exercise (Fig. 3A). During N75, [Aldo] increased markedly and end-exercise values were about 2.5-fold as high as during the other trials (P < 0.05).
The time course of ARP and [NA] during exercise was very similar (Fig. 3, B and C). ARP and [NA] increased slightly above resting value during N55 and H55. ARP and [NA] increased markedly from the first minute of exercise during H75 and N75 (P < 0.05), with higher values than during H55 and N55 from the 15th or the 30th minute of exercise for [NA] and ARP, respectively (P < 0.05). During N75, ARP and [NA] increased more markedly than during H75, with higher values from the 30th minute of exercise (P < 0.05).
DISCUSSION
The present experiment was designed to test the hypothesis that fluid-regulating hormones would depend on the relative intensity of exercise and then would be higher in hypoxia than in normoxia at the same absolute workload. Although limited to aerobically trained, young, white men, the main result reported here is that plasma levels of AVP, Aldo, and ARP increase during exercise when a threshold is reached and thereafter are dependent on the absolute workload, without any specific effect of hypoxia. The time course of ANF appears to be different from that of the other hormones.
The total water loss was not different in hypoxia and in normoxia when exercise was performed at the same absolute intensity. However, acute exposure to hypobaric hypoxia induced changes in the distribution of water loss during exercise at a given workload, with lower respiratory water loss and higher sweat loss than in normoxia. The total water loss was lower in hypoxia than in normoxia when exercise was performed at the same relative intensity, as a result of both significantly lower respiratory water loss and sweat loss. Although it has been described that in a normoxic environment, sweating depends on the absolute intensity of exercise (12,24), it appears in our experimental conditions that sweating depends on neither absolute workload nor relative intensity. Consequently, hypoxia may affect the responsiveness of sweating. Sweat glands are under sympathetic control, and even if this control is locally mediated by acetylcholine, plasma noradrenaline concentration can be a useful guide to assess sympathetic neural function during exercise (11). As previously reported (15), we observed in hypoxia a greater sympathetic activation than in normoxia at the same absolute intensity, which may have induced an increase in sweat production. As it can be assumed that heat production was the same at the same workload, it is quite surprising that such an increase in sweat loss was not associated with a different time course of rectal and mean skin temperatures during N55 and H75. It might therefore be hypothesized that the increase in sweat loss was due to an increase in trickling sweat, which is inefficient for heat dissipation. Further studies with more accurate measurement of sweat loss would be needed to elucidate this topic.
The present study shows that the concentrations of AVP, Aldo, and ARP did not change during N55 and H55, which is in good agreement with previous studies that have reported that the concentrations of those fluid-regulating hormones increase during exercise when the relative intensity reaches a threshold about 70%V̇O2max (29). The time course of ANF during H55 and N55 is also in accordance with the description of its increase at low intensity of exercise (28). Moreover, the similar time course of fluid-regulating hormones during H55 and N55 tells us that acute exposure to hypoxia has no specific effect on those hormones during moderate exercise.
More interestingly, we found that plasma levels of AVP, Aldo, and ARP were higher during N75 than H75, which shows that above the threshold for increase, the concentrations of these fluid-regulating hormones increased in a manner dependent on the absolute workload rather than the relative intensity of exercise. AVP changes occurred in response to changes in plasma osmolality, with an early increase in AVP during N75 likely attributable to an earlier increase in plasma osmolality during N75 compared with the other conditions. Although plasma osmolality was the same at the end of exercise during H75, H55, and N75, its increase occurred later in hypoxia. The time course of ARP appears to follow that of noradrenaline, as expected from what is known about the regulation of the renin-angiotensin system. More surprisingly, there appears to be a dissociation between the responses of Aldo and ARP in hypoxia. Such a dissociation has already been described (4,20) and was linked to an inhibition of the angiotensin-converting enzyme induced by hypoxia (20). Because aldosterone secretion may be inhibited by the physiological level of ANF (5), this dissociation may also have resulted from the substantial increase in ANF in hypoxia, as previously observed by others (8,21). Why ANF increased in hypoxia only when exercise was performed at high relative intensity cannot be explained by the variations in HR or plasma volume. As hemodynamic changes are the main factor involved in the acute regulation of ANF secretion, it would be very interesting to know the time course of mean arterial pressure (MAP). However, Wolfel et al. (30) previously showed that MAP was not different in hypoxia (altitude 4300 m) and in normoxia after 45 min of exercise performed at the same absolute workload corresponding to 50%V̇O2max. The high level of plasma concentration of ANF during H75 remains unclear, and further studies would be necessary to clarify the issue.
The different balance between fluid-regulating hormones induces a similar production of urine in hypoxia and in normoxia at the same absolute intensity of exercise. The increase in AVP during N75 had only a slight impact on water reabsorption, as estimated by the limited changes in calculated free water clearance (data not shown). Furthermore, the antidiuretic effect of AVP may have been counterbalanced by the diuretic effect of ANF. Although not significantly different, because of an apparent dispersion of individual values, urinary losses appeared greater in hypoxia than in normoxia at the same relative intensity of exercise. This is likely a result of greater levels of [AVP] and [Aldo] in normoxia when exercise was performed at the highest workload, associated with lower levels of [ANF], compared with hypoxia. However, it is likely that hormonal changes would have more apparent effects in urinary excretion if the period of time was longer.
In conclusion, our results indicate that acute exposure to hypobaric hypoxia had no specific effect on the time course of AVP, ARP, and Aldo during 1 h of exercise performed either at the same relative or the same absolute intensity. Plasma levels of these fluid-regulating hormones increase above a threshold of intensity and then increases occur in a manner dependent on the absolute workload.
The authors thank Dr. V. de la Guéronnière and the S.A. des Eaux minérales d’Evian for their helpful contribution.
The very valuable assistance of J. M. Cottet-Emard and A. M. Allevard (Laboratoire de Physiologie de l’environnement, Faculté de médecine Grange-Blanche, Lyon, France) is gratefully acknowledged.
The authors thank Dr. J. C. Launay, Dr. G. Savourey, A. Guinet (Département des facteurs humains, CRSSA, La Tronche, France), and J. Denis (Laboratoire d’Analyses Biologiques, CRSSA, La Tronche, France) for technical assistance.
REFERENCES
1. Bärtsch P., N. Pflüger, M. Audetat, et al. Effects of slow ascent to 4559 m on fluid homeostasis.
Aviat. Space Environ. Med. 62:105–110, 1991.
2. Beidleman, B. A., P. B. Rock, S. R. Muza, et al. Substrate oxidation is altered in women during exercise upon acute altitude exposure.
Med. Sci. Sports Exerc. 34:430–437, 2002.
3. Bouissou, P., F. Peronnet, G. Brisson, R. Helie, and M. Ledoux. Fluid-electrolyte shift and renin-aldosterone responses to exercise under hypoxia.
Horm. Metab. Res. 19:331–334, 1987.
4. Bouissou, P., C. Y. Guezennec, F. X. Galen, G. Defer, J. Fiet, and P.C. Pesquies. Dissociated response of aldosterone from plasma renin activity during prolonged exercise under hypoxia.
Horm. Metab. Res. 20:517–521, 1988.
5. Caron, N., and R. Kramp. Atrial natriuretic factor: retrospective and perspectives.
Arch. Int. Physiol. Biochim. Biophys. 102:81–95, 1994.
6. De Angelis, C., C. Ferri, L. Urbani, and S. Fabrace. Effect of acute exposure to hypoxia on electrolytes and water metabolism regulatory hormones.
Aviat. Space Environ. Med. 67:746–750, 1996.
7. Dill, D. B., and D. L. Costill. Calculation of percentage changes in volumes of blood, plasma and red cells in dehydration.
J. Appl. Physiol. 37:247–248, 1974.
8. Du Souich, P., C. Saunier, D. Hartemann, et al. Effect of moderate hypoxemia on atrial natriuretic factor and arginin vasopressin in normal man.
Biochem. Biophys. Res. Com. 148:906–912, 1987.
9. Fulco, C. S., P. B. Rock, and A. Cymerman. Maximal and submaximal exercise performance at altitude.
Aviat. Space Environ. Med. 69:793–801, 1998.
10. Gauquelin, G., and C. Gharib. Radioimmunoassay of plasma atrial natriuretic peptide: factors occurring in alterations of its concentration.
Ann. Biol. Clin. (Paris) 48:551–554, 1990.
11. Grassi, G., and M. Essler. How to assess sympathetic activity in humans.
J. Hypertens. 17:719–734, 1999.
12. Greenhaff, P. L., and P. J. Clough. Predictors of sweat loss in man during prolonged exercise.
Eur. J. Appl. Physiol. 58:348–352, 1989.
13. Greenleaf, J. E., V. A. Convertino, and G. R. Mangseth. Plasma volume during stress in man: osmolality and red cell volume.
J. Appl. Physiol. 47:1031–1038, 1979.
14. Houdas, Y., and J. Colin. Heat and water exchanges by the respiratory tract in man.
Pathol. Biol. 14:229–238, 1966.
15. Koulmann, N., B. Melin, L. Bourdon, et al. Effects of acute hypobaric hypoxia on the appearance of ingested deuterium from a deuterium-labelled carbohydrate beverage in body fluids of humans during prolonged cycling exercise.
Eur. J. Appl. Physiol. 79:397–403, 1999.
16. Lawler, J., S. K. Powers, and D. Thompson. Linear relationship between V̇O
2max and V̇O
2max decrement during exposure to acute hypoxia.
J. Appl. Physiol. 64:1486–1492, 1988.
17. Maher, J. T., L. G. Jones, H. Hartley, G. H. Williams, and L. I. Rose. Aldosterone dynamics during graded exercise at sea level and high altitude.
J. Appl. Physiol. 39:18–22, 1975.
18. Meehan, R. T. Renin, aldosterone, and vasopressin responses to hypoxia during 6 hours of mild exercise.
Aviat. Space Environ. Med. 57:960–965, 1986.
19. Milledge, J. S., E. I. Bryson, D. M. Catley, et al. Sodium balance, fluid homeostasis and the renin-aldosterone system during the prolonged exercise of hill walking.
Clin. Sci. 62:595–604, 1982.
20. Milledge, J. S., D. M. Catley, M. P. Ward, E. S. Williams, and C. R. A. Clarke. Renin-aldosterone and angiotensin-converting enzyme during prolonged altitude exposure.
J. Appl. Physiol. 55:699–702, 1983.
21. Olsen, N. V., I. L. Kanstrup, J. P. Richalet, J. M. Hansen, G. Plazen, and F. X. Galen. Effects of acute hypoxia on renal and endocrine function at rest and during graded exercise in hydrated subjects.
J. Appl. Physiol. 73:2036–2043, 1992.
22. Ramanathan, N. L. A new weighting system for mean surface temperature of the human body.
J. Appl. Physiol. 19:531–533, 1964.
23. Sagnol, M., J. Claustre, J. M. Cottet-Emard, et al. Plasma free and sulphated catecholamines after ultra-long exercise and recovery.
Eur. J. Appl. Physiol. 60:91–97, 1990.
24. Saltin, B., and B. Hermansen. Esophageal, rectal, and muscle temperature during exercise.
J. Appl. Physiol. 21:1757–1762, 1966.
25. Sawka, M. N., V. A. Convertino, E. R. Eichner, S. M. Schnieder, and A.J. Young. Blood volume: importance and adaptations to exercise training, environmental stresses, and trauma/sickness.
Med. Sci. Sports Exerc. 32:332–348, 2000.
26. Schmidt, W., G. Brabant, C. Kröger, S. Strauch and A. Hilgendorf. Atrial natriuretic peptide during and after maximal exercise and submaximal exercise under normoxic and hypoxic conditions.
Eur. J. Appl. Physiol. 61:398–407, 1990.
27. Skowsky, W. R., A. A. Rosebloom, and D. A. Fischer. Radioimmunoassay measurement of arginin-vasopressin in serum: development and application.
J. Clin. Endocrinol. Metab. 38:278–287, 1974.
28. Tanaka, H., M. Shindo, J. Gutkowska, et al. Effect of acute exercise on plasma immunoreactive-atrial natriuretic factor.
Life Sci. 39:1685–1693, 1986.
29. Wade, C. E., and J. R. Claybaugh. Plasma renin activity, vasopressin concentration, and urinary excretory responses to exercise in men.
J. Appl. Physiol. 49:930–936, 1980.
30. Wolfel, E. E., M. A. Selland, A. Cymerman, et al. O
2 extraction maintains O
2 uptake during submaximal exercise with β-adrenergic blockade at 4,300 m.
J. Appl. Physiol. 85:1092–1102, 1998.
