Hormonal responses to exercise during moderate cold exposure in young vs. middle-aged subjects A. THERMINARIAS,
P. FLORE,
M. F. ODDOU-CHIRPAZ,
C. GHARIB,
AND
G. GAUQUELIN
Centre Hospitalier regional de Grenoble, Faculte’ de Mkdecine de Grenoble, La Tronche 38.700; and, Laboratoire de Physiologie de l’environnement, Lyon 69.373, France THERMINARIAS, A., P. FLORE, M. F. ODDOU-CHIRPAZ, C. GHARIB, AND G. GAUQUELIN. Hormonal responses to exercise during moderate cold exposure in young vs. middle-aged subjects. J. Appl. Physiol. 73(4): 1564-1571, 1992.-The influence of moderate cold exposure on the hormonal responses of atria1 natriuretic factor (ANF), arginine vasopressin (AVP), catecholamines, and plasma renin activity (PRA) after exhaustive exercise was studied in 9 young and 10 middle-aged subjects. Exercise tests were randomly performed in temperate (30°C) and cold ( 10°C) environments. Heart rate, oxygen consumption, and peripheral arterial blood pressure were measured at regular intervals. Blood samples were collected before and immediately after exercise at 30 or 10°C. Plasma sodium and potassium concentrations as well as hemoglobin and hematocrit were measured, and the change in plasma volume was calculated. At rest and during exercise, oxygen consumption was similar during exposure to both temperate and cold temperatures. During submaximal exercise intensities, the rise in heart rate was blunted while the increase in systolic blood pressure was significantly greater at 10 than at 30°C. The increases in plasma sodium and potassium concentrations after exhaustion were similar between environments, as was the decrease in plasma volume. In both groups, all plasma hormones were significantly elevated postexercise, with the AVP response similar at 10 and 30°C. However, the norepinephrine and ANF responses were significantly greater while the PRA response was significantly reduced at 10°C. In the middle-aged subjects the epinephrine response to exercise was higher at 10 than at 30°C. The greater ANF and reduced PRA responses to exercise in the cold may have resulted from central hemodynamic changes caused by cold-induced cutaneous vasoconstriction. Although the alterations in hormonal concentrations are likely to have been induced by changes in central blood volume and/or blood pressure, these hormonal responses may serve as a feedback mechanism modulating the blood pressure and volume responses to both exercise and cold exposure. age; atria1 natriuretic factor; renin activity; catecholamines
arginine
vasopressin;
plasma
EXERCISE induces cardiovascular adjustments that are regulated by neural and hormonal mechanisms acting mainly on the heart, vascular smooth muscle tone, and blood volume. This extrinsic control allows the blood flow to vary in order to maintain the systemic arterial pressure at an adequate level to supply all vital organs. During short dynamic exercise, the sympathoadrenal system, via catecholamine secretion, has a dominant role in this regulation. When exercise reaches a high intensity, other hormonal factors acting on the vascular MUSCULAR
1564
0161-7567/92 $2.00 Copyright
0
tone and blood volume may be involved. Thus, high-intensity exercise is a very powerful stimulus for arginine vasopressin (AVP), atria1 natriuretic factor (ANF), and the renin-angiotensin system (4, 9, 11, 26, 30). When a muscular exercise was performed in a cold ambient temperature, the cardiovascular adjustments may be altered. Total body exposure to moderate cold induces a cutaneous vasoconstriction that reduces heat loss. Consequences of this vasoconstriction are an increase in the peripheral resistances and a shift of blood from the periphery to the core, increasing the central blood volume and ventricular filling (25). A rise in arterial pressure and a bradycardia are generally observed at rest (19). When dynamic muscular exercise is performed in cold air, the persistence of vasoconstriction may induce a cardiovascular pattern different from that observed in a temperate environment (3,8,31,32). In such conditions a greater catecholamine response is generally observed (1, 32). However, no information was available on a possible influence of peripheral vasoconstriction on the secretion of other hormonal factors involved in the control of blood volume and blood flow during exercise. Indeed, variations in ventricular filling may influence the secretion of several hormones, including AVP, ANF, and plasma renin activity (PRA). Thus the main purpose of the present study was to investigate possible effects of moderate cold exposure on the response of these hormones to exhaustive exercise. On the other hand, it has been suggested that age may influence the hormonal and hemodynamic responses to exercise (10,15) and cold exposure (34). Thus the second aim of the present study was to investigate the influence of age on these responses. Therefore, plasma AVP, ANF, PRA, and catecholrespon ses to exhaustive exercise performed in temperate (30°C) and cold (IOOC) environments were evaluated. The temperature of the cold environment was sufficient to elicit a peripheral vasoconstriction but not shivering. The plasma sodium (Na+) and potassium (K+) concentrations, plasma osmolality, and plasma volume changes were also monitored because they are linked with the hormonal variations. To study the influence of age, young and middle-aged subjects took part in the experiment. METHODS
Subjects. Nineteen male cyclists were studied in two groups according to age. The first group included nine
1992 the American
Physiological
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EXERCISE
IN
young (Y) subjects, age 19-25 yr (mean 22 t 1 yr). The second group included 10 middle-age (MA) subjects, age 40-55 yr (mean 47 t 1 yr). Subjects gave informed consent to take part in the study. For at least the last 6 yr, their main activity was cycling. An average of 10,000 km was covered yearly during training and competition. At the time of investigation, May-June, they had already done ~5,000 km. The morphological characteristics were similar in both groups: height 177 t 3 and 175 t 2 cm and weight 68 t 3 and 71 t 2 kg for Y and MA subjects, respectively. The percentage of body fat was 15 t 1 in both populations. These well-trained subjects, accustomed to carrying out high-intensity outdoor exercises, were chosen on account of cardiovascular risks incurred by untrained subjects performing an exhaustive exercise under cold conditions. Indeed, cold-induced cutaneous vasoconstriction produces an increase in myocardial 0, consumption (Vo2) related to increases in ventricular preload and afterload (3). Furthermore, cardiac arrhythmias appear frequently during exposure to cold, possibly as a result of a high catecholamine response. Therefore, before each test, electrocardiogram was recorded and blood pressure was measured. In addition and as a pretest, each subject performed an incremental exercise on a cycle ergometer, at an ambient temperature of 2O”C, until the heart rate (HR) approached the theoretical maximum HR (HR,,,; 220 - age) and, despite encouragement, the subjects could not continue. During the test, arterial blood pressure was measured at regular intervals with a sphygmomanometer. Two MA subjects whose arterial pressure response was considered as excessive were excluded [systolic blood pressure (SBP) > 250 mmHg and/or diastolic blood pressure (DBP) > 120 mmHg at any power load]. Work loads for a subsequent peak VO, (Vo2 peak)test were determined during this pretest in which maximal power output for each subject was assessed.Work loads for the . vo 2 peak test were selected to represent similar relative intensities as well as similar time to exhaustion for both the MA and the Y subjects. Experimental procedure. The subjects were asked to avoid any physical exercise the day before each test. They were studied in the morning, 2 h after ingestion of a continental breakfast that included 300 ml of fluids (no tea or coffee). The subjects were lightly dressed in shorts, shirts, and sport shoes. Tests were performed in a climatic chamber in which the temperature and the air velocity were monitored. Each participant performed two exercise tests at random: in an ambient temperature close to the neutral temperature at rest (30 t l°C) and in a moderately cold ambient temperature (10 t 1OC). The air velocity was 10 m/s during both tests. Before each test, subjects were weighed naked and the rectal temperature was measured with a mercury thermometer. A small Teflon catheter was inserted into a cubital vein to allow blood sampling. To prevent clotting, the catheter was flushed once with heparinized normal saline; no further flushing was necessary. Subjects remained seated for 10 min while electrodes were placed on the chest to measure the HR, and four skin thermistors were attached (thorax, forearm, anterior thigh, and anterior lower leg) for the determination of the mean cutaneous temperature. Then
THE
1565
COLD
the subjects entered the climatic chamber and sat on the bicycle. Five minutes later, control values were set up, and, with a control position of the arm height, a 15-ml blood sample was drawn and collected in specific chilled tubes for the determination of biological values. The subjects then began to pedal for 3 min against no resistance, after which the exercise intensity was increased every 3 min until the HR approached the theoretical HR,,, (220- age) and, despite encouragement, the subject could not continue. Because the estimated Vo2peak is lower in MA than in Y subjects and to obtain a similar duration of cold exposure, increments were 35 W in Y and 30 W in MA subjects obtained by 70 and 60 rpm, respectively. The VO, was determined by the Douglas bag method: a collection was performed at rest just before the start of the exercise and during the 3rd min of each exercise intensity. If the subject could not complete the entire measurement at the maximal intensity, the sample was Sollected for as long as he could continue. The highest VO, recorded during the test was considered to be the VO, Expired 0, and CO, concentrations were measured with Beckman OM-11 and LB2 analyzers, respectively, calibrated with gases of known concentrations before each test. Expired volumes were measured with a Tissot spirometer. The HR and cutaneous temperatures were continuously recorded. Arterial blood pressure was always measured by the same investigator using a sphygmomanometer that was calibrated with a mercury column at rest and the last minute of each work load. At the end of the test, rectal temperature was measured again. Biological values. A 15-ml blood sample was collected at rest and within 1 min after exhaustion to determine the plasma concentration of epinephrine (EPI), norepinephrine (NOR) (6), AVP (28), ANF (12), and PRA (33) as well as the Na+, K+, and plasma lactate (17) concentrations. Radioimmunoassay of AVP was performed on extracted plasma (bentonite), and the assay sensitivity is 0.3 pg/ml. The recovery of AVP was 75% and intra- and interassay coefficients of variation were 3 and ll%, respectively. The antibodies were a gift of L. Keil. The ANF radioimmunoassay was made after extraction with octadecylsilyl cartridges (Sep-Pak). The antibodies were a gift of J. Gutkowska. The recovery for added ANF was 85%. Intra- and interassay coefficients of variation were 10% and sensitivity was 1.2 pg/ml. The PRA was measured with antibodies raised in the laboratory (pH 7.4, incubation 16 h). Intra- and interassay coefficients of variation were 1 and 2.5%, respectively, and sensitivity was 20 pg 1-l min? A small quantity of blood was drawn during the last minute of each step for hematocrit and hemoglobin determinations. The microhematocrit was determined in duplicate by centrifugation. The values were not corrected for trapped plasma. The hemoglobin was measured on a CO-oximeter 282, Na+ and K+ on a SMAC-2 Technicon autoanalyzer, and osmolality on a Fiske OR photometer. Calculation and statistics. The plasma volume changes were assessed from hematocrit and hemoglobin values (7). The mean cutaneous temperature was computed according to Ramanathan’s equation (23). Dependent measures (HR, SBP, and DBP) taken durpeak
l
l
l
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1566
EXERCISE
Rest
A-
200
‘I
180
Submaximal intensities
IN THE
h2peak
‘E 160 ;
140
ii -120 a z L 100 Y s
I”
80
!
’
35
’
’
105
’
’ 175
’
’ 24s
’
’
’
’
385
315
B 200 : 180 -C F ‘e 160
1 L”““““’
COLD
sure and the VO, was identical in both environments. Mean cutaneous temperature and HR were lower after 5 min of cold exposure than at 30°C. The SBP was higher at 10 than at 3O”C, while the change in DBP was not significant. Values obtained in Y subjects were similar to those obtained in MA subjects. When the exercise intensity was submaximal, the Vo2 was identical in both environments. As expected, HR and SBP significantly increased, with the magnitude of the response directly related to exercise intensity. DBP was not significantly altered. There was a main effect of temperature on HR (P < 0.001) and SBP (P < 0.001). The HR was lower and the SBP higher at 10 than at 30°C in both groups. The DBP was accurately determined only in seven Y subjects for exercise intensities >l50 W and in eight MA subjects for exercise intensities ~175 W. There was a main effect of temperature on DBP, higher at 10 than 30°C (P < 0.05). This effect was significant only in the MA subjects. There was a main effect of age on HR (P < 0.001): HR was lower in MA than in Y subjects at 30 and 10°C. There was also a main effect of age on DBP (P < O.OOl), lower in Y than in MA subjects in both environments. No main effect of age was found for SBP. For a given subject, the change in SBP induced by cold expoSubmaximal intensities
Rest
30
90
150
210
270
\iO 2pc3k
300
Work rate (watt) FIG. 1. Heart rate (HR) at rest, during submaximal exercise, and at exhaustion in young (Y, n = 9; A) and middle-aged subjects (MA, n = 10; B) at 10 and 30°C ambient temperatures. Values are means & SE. vo 2pe,, peak 0, consumption. * P < 0.02, 10 vs. 30°C in each group; o P < 0.02, Y vs. MA at 30°C; l P < 0.02, Y vs. MA at 10°C. During submaximal exercise, HR was lower at 10 than at 30°C in Y and MA (P < 0.001) and lower in MA than in Y at 10 and 30°C (P < 0.001).
ing exercise were analyzed separately by means of a three-way analysis of variance (ANOVA) with repeated measures for main effects and interactions across independent measures (ANOVA; age X temperature X time). All data obtained at rest and after exercise were analyzed by repeated-measures two-way ANOVA, the two factors taken into account being temperature and age. In the event that the F value of ANOVA was significant, post hoc analysis was carried out using the Bonferroni method of multiple comparisons (35). The Student’s t test for paired observation was used to determine whether significant differences occurred between values obtained at rest and after exercise. Before statistical analysis, the plasma EPI values were converted to log,, values. This transformation was performed because of the nonhomogeneity of variance in plasma EPI concentrations. The accepted level of significance of all statistical tests was set at 5%. Data are means t SE. RESULTS
Physiological parameters. The HR values are given in
Fig. 1, the arterial pressure in Fig. 2, and other values in Table 1. At rest, no shivering was observed during cold expo-
105
35
B
175
245
315
300
385 +
‘bi,
X
E wE 200 2 3 z 2 za 100 .I
r
sBp
*=
+ 1
+
+
5 s I
30
1
1
90
Work
I
I
150
’
1
210
270
300
rate (watt)
FIG. 2. Systolic (SBP) and diastolic (DBP) blood pressures at rest, during submaximal exercise, and at exhaustion in Y (A) and MA (B) at 10 and 30°C ambient temperatures. Values are means ~frSE. * P < 0.05, 10°C vs. 30°C in each group; o P-c 0.05, Y vs. MA at 30°C; l P < 0.05, Y vs. MA at 10°C. During submaximal exercise, SBP was higher at 10 than at 30°C in Y and MA (P < 0.001).
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EXERCISE
IN
1. Physiological parameters and plasma lactate level
TABLE
h
ml kg-’ - min-’ l
T re9 “C
T,, “C
Lactate, mm01 A
Rest Young 30°C 10°C Middle-aged 30°C 10°C
4.6kO.6 5.4kO.5
37.3kO.2 37.2t0.2
4.9kO.5 4.5kO.5
37.0&O. 1 37.1kO.l
’
33.2kO.3 30.6&0.7*
1.9tO.l 1.7kO.2
33.020.5 29.2*0.3*
1.4kO.l 1.3kO.l
38.2tO.l 38.0&O. 1
32.5H.6 27.9+2.1?
11.4kl.O 11.6tl.l
37.7&O. 1 37.2-tO.l*$
33.2tl.O 27.521.4-t
THE
COLD
1567
cantly elevated after exhaustion (Figs. 4 and 5). In both groups, the AVP plasma concentrations at 10°C were similar to those at 30°C (Fig. 5), whereas the NOR (Fig. 4) and ANF (Fig. 5) plasma concentrations at 10°C were higher than those at 30°C. On the other hand, the PRA measured at 10°C was lower than that at 30°C (Fig. 5). The EPI plasma concentrations were higher at 10 than at 30°C only in MA subjects. Thus EPI plasma levels postexercise at 10°C were higher in MA than in Y subjects. Other hormonal values obtained in MA subjects were not significantly different from those obtained in Y subjects.
Exhaustion Young 30°C 10°C Middle-aged 30°C 10°C
DISCUSSION 67.8d.5 70.4d.5 49.8k2.93 52.3+3.5§
8.0*0.6$ 7.8+0.2$
Values are means + SE of 9 young and 10 middle-aged-subjects at rest and exhaustion at 30 and 10°C ambient temperatures. VO,, oxygen consumption; T,, , rectal temperature; T,, mean cutaneous temperature. 10 vs. 30°C: * P < 0.05, “f P < 0.02. Young vs. middle-aged: $P < 0.05, Q P < 0.01.
sure, that is, the difference between the SBP measured at 10°C and that measured at 3O”C, did not greatly vary whatever the exercise intensity. However, there was a wide vari ation from one subject to another. Thus, for each subjec t, this difference was calcula ted for all intensities and a mean value of SBP variation was de termined. From this mean variation, subjects could be classified as nonreactive, moderately reactive, or hyperreactive to cold exposure (>20 mmHg at 10°C; Fig. 3). The reactivity did not appear to be related to aging. At exhaustion in both groups, vo2 peak, HR,,,, and DBP were similar at 10 and 30°C (Figs. 1 and 2). The SBP remained higher and the mean cutaneous temperature lower at 10 than at 30°C. All subjects showed an increase in rectal temperature with exercise (Table 1). However, in MA subjects, rectal temperature at 10°C was lower than that at 30°C. At 3O”C, the duration of exercise was 33 t 1 min for Y and 29 t 1 min for MA subjects. In both groups, the duration of exercise at 10°C was similar to that at 30°C. As expected, the VOW,,, and HR,,, were higher in Y than in MA subjects. Blood variables. At rest, the MA subjects had higher plasma osmolalities than the Y subjects under both ambient temperatures (Table 2). They had significantly higher Na+ and K+ plasma concentrations only at 30°C. The NOR was significantly higher at 10 than at 30°C in both groups (Fig. 4). All other blood variables were identical at rest under both environments and did not differ significantly in Y compared with MA subjects (Table 2, Figs. 4 and 5). During exercise, hematocrit and hemoglobin concentration progressively and similarly increased in both environments in both groups. hematocrit and hem .oglobin values At exhaustion, were significantly increased compared with rest and plasma volume was decreased. This decrease was similar in both groups and in both environmental conditions (Table 2). All plasma hormone concentrations were signifi-
The present study compares the interactive effects of a moderate cold exposure and exhaustive muscular exercise on the ANF, AVP, PRA, NOR, and EPI responses in Y and MA subjects. We found that cold exposure affects the ANF, PRA, and NOR responses during exercise and that this effect was not influenced by aging. Cold exposure affects the EPI response during exhaustive exercise only in MA subjects. In this study, only endurance-trained subjects were used. The potential effects of physical fitness levels on cold tolerance remain in question (34). Results might have been different with untrained subjects. Thus, most parameters measured at rest were similar in both groups, probably because of the volume of training performed by MA subjects. In particular, arterial pressure was not higher in MA than in Y subjects, as related in other studies (10). However, despite the same fluid ingestion before exercise, plasma osmolalities measured at rest were higher in the MA than in the Y subjects. This may indicate that the MA subjects were relatively dehydrated before exercise. Evidence suggests that older men are prone to hyperosmolar hypohydration (22). This may result from a decreased thirst sensitivity and/or a limited ability of the kidneys to concentrate urine, which might lead to enhanced free water excretion (22). This may have altered both the blood pressure and hormonal responses of MA subjects. During exposure of the whole body to cold air, the first response is a peripheral vasoconstriction, which reduces heat loss. If this mechanism remains insufficient, shivering thermogenesis occurs, which increases the heat production (19). In this experiment, a moderately cold temperature and a short duration of exposure were chosen to study only the effect of peripheral vasoconstriction. The presence of this mechanism was reflected by the lower mean cutaneous temperature obtained 5 min after exposure to cold. No shivering occurred, as indicated by the same resting VO, found under both ambient conditions. Consequences of cutaneous vasoconstriction are an increase in peripheral resistances and a shift of blood from the periphery to the core, increasing central blood volume and ventricular filling (25). These effects were reflected by the bradycardia and the rise in SBP measured 5 min after exposure to cold. Simultaneously, a slight increase in NOR plasma concentration was found. An increase in NOR plasma concentration is generally thought to reflect an increase in the activity of the sympa-
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1568 TABLE
EXERCISE
IN
THE
COLD
2. Biological values Na+, mmol/l
K’,
Osmolality, mosmol/kgH,O
mmol/l
Hct,
%PCV
% APV
Rest Young 30°C 10°C Middle-aged 30°C 10°C
137.9+0.8 139.9+0.9
4.3+0.1 4.320.1
285.4k1.3 289.Okl.O
43.8kO.7 43.8-t0.7
140.8+0.6$ 140.4kO.8
4.8&0.1§ 4.6tO.l
293.4+1.3§ 292.5+_1.7$
44.7kO.7 44.4kO.4
Exhaustion Young 30°C 10°C Middle-aged 3o”c 10°C
140.4+0.5* 142.9+0.8*
4.5-to.1* 4.7-tO.2*
292.5+1.1? 297.4*1.5?
47.2+0.8? 48.1&0.9?
-12.8k1.9 -14.9k1.2
141.7+0.7* 142.OkO.8”
5.0tO.l* 4.8&0.1*
296.O-t1.7* 296.5& 1.9.t
47.2+0.8? 48.1+0.9?
-14.4k1.7 -1l.lk1.6
Values are means + SE of 9 young and 10 middle-aged subjects at rest and exhaustion at 30 and 10°C ambient temperatures. sodium; K+, plasma potassium; Hct, hematocrit; % APV, percent change in plasma volume; %PCV, percent packed cell volume. rest: * P < 0.05, “f P < 0.02. Middle-aged vs. young: $ P < 0.05, Q P < 0.01. There was no difference between conditions.
thetic nervous system. This increase was probably responsible for the cutaneous vasoconstriction. The plasma levels of the other hormones we studied were unaffected by the cold temperature, possibly because of the short time of exposure. Exhaustive exercise caused an increase in all plasma hormone concentrations measured under both ambient conditions. At the temperate ambient temperature, the magnitude of hormonal response is consistent with other studies using exercises of similar duration and intensity (9,24,26). In our study, this response was not influenced by aging. In particular, the ANF response was not significantly different in Y and MA subjects. Recently, Freund et al. (10) found a higher ANF plasma concentration in MA than in Y athletes during a marathon, after 10 km of running. The proposed mechanism is an exaggerated response to central blood volume expansion in older subjects. Differences in type, intensity, and duration of exercise may explain the discrepancy observed between the studies. Furthermore, Freund et al. reported higher resting blood pressure values in the MA than in the Y subjects, whereas no difference in resting blood pressure was found in our populations. Perhaps differences in blood L
Na+, plasma Exhaustion vs.
pressure, and presumably central volume responses, contribute to the difference between studies. Moderate cold exposure induced a further increase in the plasma NOR concentration obtained at exhaustion. This result is in agreement with the higher plasma catecholamine level previously observed when exercise was performed in cold air (1, 32). This further rise probably has a role in particular cardiovascular adjustments generally observed under this condition. Thus, for a given exercise intensity, the blood pressure is higher; the cardiac output is not influenced by cold exposure but is obtained by a lower HR and a greater systolic volume (3, 8, 31). Exhaustion
Rest
l
+
I
P
1
7n
YO"W middle-aged l
A
Young I middle-aged
hyper-reactive
moderately
reactive
FIG.
30°C
3. Individual differences (means + SE) between for all submaximal exercise intensities.
SBP at 10 and
FIG. 4. Epinephrine (EPI) and norepinephrine (NOR) plasma centrations at rest and exhaustion in Y (n = 8) and MA (n = 10) at 30 and 10°C ambient temperatures. Values are means t SE. 0.05, exhaustion vs. rest; .P< 0.05,10vs.30°C;oP
P. FLORE,
M. F. ODDOU-CHIRPAZ,
C. GHARIB,
AND
G. GAUQUELIN
Centre Hospitalier regional de Grenoble, Faculte’ de Mkdecine de Grenoble, La Tronche 38.700; and, Laboratoire de Physiologie de l’environnement, Lyon 69.373, France THERMINARIAS, A., P. FLORE, M. F. ODDOU-CHIRPAZ, C. GHARIB, AND G. GAUQUELIN. Hormonal responses to exercise during moderate cold exposure in young vs. middle-aged subjects. J. Appl. Physiol. 73(4): 1564-1571, 1992.-The influence of moderate cold exposure on the hormonal responses of atria1 natriuretic factor (ANF), arginine vasopressin (AVP), catecholamines, and plasma renin activity (PRA) after exhaustive exercise was studied in 9 young and 10 middle-aged subjects. Exercise tests were randomly performed in temperate (30°C) and cold ( 10°C) environments. Heart rate, oxygen consumption, and peripheral arterial blood pressure were measured at regular intervals. Blood samples were collected before and immediately after exercise at 30 or 10°C. Plasma sodium and potassium concentrations as well as hemoglobin and hematocrit were measured, and the change in plasma volume was calculated. At rest and during exercise, oxygen consumption was similar during exposure to both temperate and cold temperatures. During submaximal exercise intensities, the rise in heart rate was blunted while the increase in systolic blood pressure was significantly greater at 10 than at 30°C. The increases in plasma sodium and potassium concentrations after exhaustion were similar between environments, as was the decrease in plasma volume. In both groups, all plasma hormones were significantly elevated postexercise, with the AVP response similar at 10 and 30°C. However, the norepinephrine and ANF responses were significantly greater while the PRA response was significantly reduced at 10°C. In the middle-aged subjects the epinephrine response to exercise was higher at 10 than at 30°C. The greater ANF and reduced PRA responses to exercise in the cold may have resulted from central hemodynamic changes caused by cold-induced cutaneous vasoconstriction. Although the alterations in hormonal concentrations are likely to have been induced by changes in central blood volume and/or blood pressure, these hormonal responses may serve as a feedback mechanism modulating the blood pressure and volume responses to both exercise and cold exposure. age; atria1 natriuretic factor; renin activity; catecholamines
arginine
vasopressin;
plasma
EXERCISE induces cardiovascular adjustments that are regulated by neural and hormonal mechanisms acting mainly on the heart, vascular smooth muscle tone, and blood volume. This extrinsic control allows the blood flow to vary in order to maintain the systemic arterial pressure at an adequate level to supply all vital organs. During short dynamic exercise, the sympathoadrenal system, via catecholamine secretion, has a dominant role in this regulation. When exercise reaches a high intensity, other hormonal factors acting on the vascular MUSCULAR
1564
0161-7567/92 $2.00 Copyright
0
tone and blood volume may be involved. Thus, high-intensity exercise is a very powerful stimulus for arginine vasopressin (AVP), atria1 natriuretic factor (ANF), and the renin-angiotensin system (4, 9, 11, 26, 30). When a muscular exercise was performed in a cold ambient temperature, the cardiovascular adjustments may be altered. Total body exposure to moderate cold induces a cutaneous vasoconstriction that reduces heat loss. Consequences of this vasoconstriction are an increase in the peripheral resistances and a shift of blood from the periphery to the core, increasing the central blood volume and ventricular filling (25). A rise in arterial pressure and a bradycardia are generally observed at rest (19). When dynamic muscular exercise is performed in cold air, the persistence of vasoconstriction may induce a cardiovascular pattern different from that observed in a temperate environment (3,8,31,32). In such conditions a greater catecholamine response is generally observed (1, 32). However, no information was available on a possible influence of peripheral vasoconstriction on the secretion of other hormonal factors involved in the control of blood volume and blood flow during exercise. Indeed, variations in ventricular filling may influence the secretion of several hormones, including AVP, ANF, and plasma renin activity (PRA). Thus the main purpose of the present study was to investigate possible effects of moderate cold exposure on the response of these hormones to exhaustive exercise. On the other hand, it has been suggested that age may influence the hormonal and hemodynamic responses to exercise (10,15) and cold exposure (34). Thus the second aim of the present study was to investigate the influence of age on these responses. Therefore, plasma AVP, ANF, PRA, and catecholrespon ses to exhaustive exercise performed in temperate (30°C) and cold (IOOC) environments were evaluated. The temperature of the cold environment was sufficient to elicit a peripheral vasoconstriction but not shivering. The plasma sodium (Na+) and potassium (K+) concentrations, plasma osmolality, and plasma volume changes were also monitored because they are linked with the hormonal variations. To study the influence of age, young and middle-aged subjects took part in the experiment. METHODS
Subjects. Nineteen male cyclists were studied in two groups according to age. The first group included nine
1992 the American
Physiological
Society
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EXERCISE
IN
young (Y) subjects, age 19-25 yr (mean 22 t 1 yr). The second group included 10 middle-age (MA) subjects, age 40-55 yr (mean 47 t 1 yr). Subjects gave informed consent to take part in the study. For at least the last 6 yr, their main activity was cycling. An average of 10,000 km was covered yearly during training and competition. At the time of investigation, May-June, they had already done ~5,000 km. The morphological characteristics were similar in both groups: height 177 t 3 and 175 t 2 cm and weight 68 t 3 and 71 t 2 kg for Y and MA subjects, respectively. The percentage of body fat was 15 t 1 in both populations. These well-trained subjects, accustomed to carrying out high-intensity outdoor exercises, were chosen on account of cardiovascular risks incurred by untrained subjects performing an exhaustive exercise under cold conditions. Indeed, cold-induced cutaneous vasoconstriction produces an increase in myocardial 0, consumption (Vo2) related to increases in ventricular preload and afterload (3). Furthermore, cardiac arrhythmias appear frequently during exposure to cold, possibly as a result of a high catecholamine response. Therefore, before each test, electrocardiogram was recorded and blood pressure was measured. In addition and as a pretest, each subject performed an incremental exercise on a cycle ergometer, at an ambient temperature of 2O”C, until the heart rate (HR) approached the theoretical maximum HR (HR,,,; 220 - age) and, despite encouragement, the subjects could not continue. During the test, arterial blood pressure was measured at regular intervals with a sphygmomanometer. Two MA subjects whose arterial pressure response was considered as excessive were excluded [systolic blood pressure (SBP) > 250 mmHg and/or diastolic blood pressure (DBP) > 120 mmHg at any power load]. Work loads for a subsequent peak VO, (Vo2 peak)test were determined during this pretest in which maximal power output for each subject was assessed.Work loads for the . vo 2 peak test were selected to represent similar relative intensities as well as similar time to exhaustion for both the MA and the Y subjects. Experimental procedure. The subjects were asked to avoid any physical exercise the day before each test. They were studied in the morning, 2 h after ingestion of a continental breakfast that included 300 ml of fluids (no tea or coffee). The subjects were lightly dressed in shorts, shirts, and sport shoes. Tests were performed in a climatic chamber in which the temperature and the air velocity were monitored. Each participant performed two exercise tests at random: in an ambient temperature close to the neutral temperature at rest (30 t l°C) and in a moderately cold ambient temperature (10 t 1OC). The air velocity was 10 m/s during both tests. Before each test, subjects were weighed naked and the rectal temperature was measured with a mercury thermometer. A small Teflon catheter was inserted into a cubital vein to allow blood sampling. To prevent clotting, the catheter was flushed once with heparinized normal saline; no further flushing was necessary. Subjects remained seated for 10 min while electrodes were placed on the chest to measure the HR, and four skin thermistors were attached (thorax, forearm, anterior thigh, and anterior lower leg) for the determination of the mean cutaneous temperature. Then
THE
1565
COLD
the subjects entered the climatic chamber and sat on the bicycle. Five minutes later, control values were set up, and, with a control position of the arm height, a 15-ml blood sample was drawn and collected in specific chilled tubes for the determination of biological values. The subjects then began to pedal for 3 min against no resistance, after which the exercise intensity was increased every 3 min until the HR approached the theoretical HR,,, (220- age) and, despite encouragement, the subject could not continue. Because the estimated Vo2peak is lower in MA than in Y subjects and to obtain a similar duration of cold exposure, increments were 35 W in Y and 30 W in MA subjects obtained by 70 and 60 rpm, respectively. The VO, was determined by the Douglas bag method: a collection was performed at rest just before the start of the exercise and during the 3rd min of each exercise intensity. If the subject could not complete the entire measurement at the maximal intensity, the sample was Sollected for as long as he could continue. The highest VO, recorded during the test was considered to be the VO, Expired 0, and CO, concentrations were measured with Beckman OM-11 and LB2 analyzers, respectively, calibrated with gases of known concentrations before each test. Expired volumes were measured with a Tissot spirometer. The HR and cutaneous temperatures were continuously recorded. Arterial blood pressure was always measured by the same investigator using a sphygmomanometer that was calibrated with a mercury column at rest and the last minute of each work load. At the end of the test, rectal temperature was measured again. Biological values. A 15-ml blood sample was collected at rest and within 1 min after exhaustion to determine the plasma concentration of epinephrine (EPI), norepinephrine (NOR) (6), AVP (28), ANF (12), and PRA (33) as well as the Na+, K+, and plasma lactate (17) concentrations. Radioimmunoassay of AVP was performed on extracted plasma (bentonite), and the assay sensitivity is 0.3 pg/ml. The recovery of AVP was 75% and intra- and interassay coefficients of variation were 3 and ll%, respectively. The antibodies were a gift of L. Keil. The ANF radioimmunoassay was made after extraction with octadecylsilyl cartridges (Sep-Pak). The antibodies were a gift of J. Gutkowska. The recovery for added ANF was 85%. Intra- and interassay coefficients of variation were 10% and sensitivity was 1.2 pg/ml. The PRA was measured with antibodies raised in the laboratory (pH 7.4, incubation 16 h). Intra- and interassay coefficients of variation were 1 and 2.5%, respectively, and sensitivity was 20 pg 1-l min? A small quantity of blood was drawn during the last minute of each step for hematocrit and hemoglobin determinations. The microhematocrit was determined in duplicate by centrifugation. The values were not corrected for trapped plasma. The hemoglobin was measured on a CO-oximeter 282, Na+ and K+ on a SMAC-2 Technicon autoanalyzer, and osmolality on a Fiske OR photometer. Calculation and statistics. The plasma volume changes were assessed from hematocrit and hemoglobin values (7). The mean cutaneous temperature was computed according to Ramanathan’s equation (23). Dependent measures (HR, SBP, and DBP) taken durpeak
l
l
l
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1566
EXERCISE
Rest
A-
200
‘I
180
Submaximal intensities
IN THE
h2peak
‘E 160 ;
140
ii -120 a z L 100 Y s
I”
80
!
’
35
’
’
105
’
’ 175
’
’ 24s
’
’
’
’
385
315
B 200 : 180 -C F ‘e 160
1 L”““““’
COLD
sure and the VO, was identical in both environments. Mean cutaneous temperature and HR were lower after 5 min of cold exposure than at 30°C. The SBP was higher at 10 than at 3O”C, while the change in DBP was not significant. Values obtained in Y subjects were similar to those obtained in MA subjects. When the exercise intensity was submaximal, the Vo2 was identical in both environments. As expected, HR and SBP significantly increased, with the magnitude of the response directly related to exercise intensity. DBP was not significantly altered. There was a main effect of temperature on HR (P < 0.001) and SBP (P < 0.001). The HR was lower and the SBP higher at 10 than at 30°C in both groups. The DBP was accurately determined only in seven Y subjects for exercise intensities >l50 W and in eight MA subjects for exercise intensities ~175 W. There was a main effect of temperature on DBP, higher at 10 than 30°C (P < 0.05). This effect was significant only in the MA subjects. There was a main effect of age on HR (P < 0.001): HR was lower in MA than in Y subjects at 30 and 10°C. There was also a main effect of age on DBP (P < O.OOl), lower in Y than in MA subjects in both environments. No main effect of age was found for SBP. For a given subject, the change in SBP induced by cold expoSubmaximal intensities
Rest
30
90
150
210
270
\iO 2pc3k
300
Work rate (watt) FIG. 1. Heart rate (HR) at rest, during submaximal exercise, and at exhaustion in young (Y, n = 9; A) and middle-aged subjects (MA, n = 10; B) at 10 and 30°C ambient temperatures. Values are means & SE. vo 2pe,, peak 0, consumption. * P < 0.02, 10 vs. 30°C in each group; o P < 0.02, Y vs. MA at 30°C; l P < 0.02, Y vs. MA at 10°C. During submaximal exercise, HR was lower at 10 than at 30°C in Y and MA (P < 0.001) and lower in MA than in Y at 10 and 30°C (P < 0.001).
ing exercise were analyzed separately by means of a three-way analysis of variance (ANOVA) with repeated measures for main effects and interactions across independent measures (ANOVA; age X temperature X time). All data obtained at rest and after exercise were analyzed by repeated-measures two-way ANOVA, the two factors taken into account being temperature and age. In the event that the F value of ANOVA was significant, post hoc analysis was carried out using the Bonferroni method of multiple comparisons (35). The Student’s t test for paired observation was used to determine whether significant differences occurred between values obtained at rest and after exercise. Before statistical analysis, the plasma EPI values were converted to log,, values. This transformation was performed because of the nonhomogeneity of variance in plasma EPI concentrations. The accepted level of significance of all statistical tests was set at 5%. Data are means t SE. RESULTS
Physiological parameters. The HR values are given in
Fig. 1, the arterial pressure in Fig. 2, and other values in Table 1. At rest, no shivering was observed during cold expo-
105
35
B
175
245
315
300
385 +
‘bi,
X
E wE 200 2 3 z 2 za 100 .I
r
sBp
*=
+ 1
+
+
5 s I
30
1
1
90
Work
I
I
150
’
1
210
270
300
rate (watt)
FIG. 2. Systolic (SBP) and diastolic (DBP) blood pressures at rest, during submaximal exercise, and at exhaustion in Y (A) and MA (B) at 10 and 30°C ambient temperatures. Values are means ~frSE. * P < 0.05, 10°C vs. 30°C in each group; o P-c 0.05, Y vs. MA at 30°C; l P < 0.05, Y vs. MA at 10°C. During submaximal exercise, SBP was higher at 10 than at 30°C in Y and MA (P < 0.001).
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EXERCISE
IN
1. Physiological parameters and plasma lactate level
TABLE
h
ml kg-’ - min-’ l
T re9 “C
T,, “C
Lactate, mm01 A
Rest Young 30°C 10°C Middle-aged 30°C 10°C
4.6kO.6 5.4kO.5
37.3kO.2 37.2t0.2
4.9kO.5 4.5kO.5
37.0&O. 1 37.1kO.l
’
33.2kO.3 30.6&0.7*
1.9tO.l 1.7kO.2
33.020.5 29.2*0.3*
1.4kO.l 1.3kO.l
38.2tO.l 38.0&O. 1
32.5H.6 27.9+2.1?
11.4kl.O 11.6tl.l
37.7&O. 1 37.2-tO.l*$
33.2tl.O 27.521.4-t
THE
COLD
1567
cantly elevated after exhaustion (Figs. 4 and 5). In both groups, the AVP plasma concentrations at 10°C were similar to those at 30°C (Fig. 5), whereas the NOR (Fig. 4) and ANF (Fig. 5) plasma concentrations at 10°C were higher than those at 30°C. On the other hand, the PRA measured at 10°C was lower than that at 30°C (Fig. 5). The EPI plasma concentrations were higher at 10 than at 30°C only in MA subjects. Thus EPI plasma levels postexercise at 10°C were higher in MA than in Y subjects. Other hormonal values obtained in MA subjects were not significantly different from those obtained in Y subjects.
Exhaustion Young 30°C 10°C Middle-aged 30°C 10°C
DISCUSSION 67.8d.5 70.4d.5 49.8k2.93 52.3+3.5§
8.0*0.6$ 7.8+0.2$
Values are means + SE of 9 young and 10 middle-aged-subjects at rest and exhaustion at 30 and 10°C ambient temperatures. VO,, oxygen consumption; T,, , rectal temperature; T,, mean cutaneous temperature. 10 vs. 30°C: * P < 0.05, “f P < 0.02. Young vs. middle-aged: $P < 0.05, Q P < 0.01.
sure, that is, the difference between the SBP measured at 10°C and that measured at 3O”C, did not greatly vary whatever the exercise intensity. However, there was a wide vari ation from one subject to another. Thus, for each subjec t, this difference was calcula ted for all intensities and a mean value of SBP variation was de termined. From this mean variation, subjects could be classified as nonreactive, moderately reactive, or hyperreactive to cold exposure (>20 mmHg at 10°C; Fig. 3). The reactivity did not appear to be related to aging. At exhaustion in both groups, vo2 peak, HR,,,, and DBP were similar at 10 and 30°C (Figs. 1 and 2). The SBP remained higher and the mean cutaneous temperature lower at 10 than at 30°C. All subjects showed an increase in rectal temperature with exercise (Table 1). However, in MA subjects, rectal temperature at 10°C was lower than that at 30°C. At 3O”C, the duration of exercise was 33 t 1 min for Y and 29 t 1 min for MA subjects. In both groups, the duration of exercise at 10°C was similar to that at 30°C. As expected, the VOW,,, and HR,,, were higher in Y than in MA subjects. Blood variables. At rest, the MA subjects had higher plasma osmolalities than the Y subjects under both ambient temperatures (Table 2). They had significantly higher Na+ and K+ plasma concentrations only at 30°C. The NOR was significantly higher at 10 than at 30°C in both groups (Fig. 4). All other blood variables were identical at rest under both environments and did not differ significantly in Y compared with MA subjects (Table 2, Figs. 4 and 5). During exercise, hematocrit and hemoglobin concentration progressively and similarly increased in both environments in both groups. hematocrit and hem .oglobin values At exhaustion, were significantly increased compared with rest and plasma volume was decreased. This decrease was similar in both groups and in both environmental conditions (Table 2). All plasma hormone concentrations were signifi-
The present study compares the interactive effects of a moderate cold exposure and exhaustive muscular exercise on the ANF, AVP, PRA, NOR, and EPI responses in Y and MA subjects. We found that cold exposure affects the ANF, PRA, and NOR responses during exercise and that this effect was not influenced by aging. Cold exposure affects the EPI response during exhaustive exercise only in MA subjects. In this study, only endurance-trained subjects were used. The potential effects of physical fitness levels on cold tolerance remain in question (34). Results might have been different with untrained subjects. Thus, most parameters measured at rest were similar in both groups, probably because of the volume of training performed by MA subjects. In particular, arterial pressure was not higher in MA than in Y subjects, as related in other studies (10). However, despite the same fluid ingestion before exercise, plasma osmolalities measured at rest were higher in the MA than in the Y subjects. This may indicate that the MA subjects were relatively dehydrated before exercise. Evidence suggests that older men are prone to hyperosmolar hypohydration (22). This may result from a decreased thirst sensitivity and/or a limited ability of the kidneys to concentrate urine, which might lead to enhanced free water excretion (22). This may have altered both the blood pressure and hormonal responses of MA subjects. During exposure of the whole body to cold air, the first response is a peripheral vasoconstriction, which reduces heat loss. If this mechanism remains insufficient, shivering thermogenesis occurs, which increases the heat production (19). In this experiment, a moderately cold temperature and a short duration of exposure were chosen to study only the effect of peripheral vasoconstriction. The presence of this mechanism was reflected by the lower mean cutaneous temperature obtained 5 min after exposure to cold. No shivering occurred, as indicated by the same resting VO, found under both ambient conditions. Consequences of cutaneous vasoconstriction are an increase in peripheral resistances and a shift of blood from the periphery to the core, increasing central blood volume and ventricular filling (25). These effects were reflected by the bradycardia and the rise in SBP measured 5 min after exposure to cold. Simultaneously, a slight increase in NOR plasma concentration was found. An increase in NOR plasma concentration is generally thought to reflect an increase in the activity of the sympa-
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1568 TABLE
EXERCISE
IN
THE
COLD
2. Biological values Na+, mmol/l
K’,
Osmolality, mosmol/kgH,O
mmol/l
Hct,
%PCV
% APV
Rest Young 30°C 10°C Middle-aged 30°C 10°C
137.9+0.8 139.9+0.9
4.3+0.1 4.320.1
285.4k1.3 289.Okl.O
43.8kO.7 43.8-t0.7
140.8+0.6$ 140.4kO.8
4.8&0.1§ 4.6tO.l
293.4+1.3§ 292.5+_1.7$
44.7kO.7 44.4kO.4
Exhaustion Young 30°C 10°C Middle-aged 3o”c 10°C
140.4+0.5* 142.9+0.8*
4.5-to.1* 4.7-tO.2*
292.5+1.1? 297.4*1.5?
47.2+0.8? 48.1&0.9?
-12.8k1.9 -14.9k1.2
141.7+0.7* 142.OkO.8”
5.0tO.l* 4.8&0.1*
296.O-t1.7* 296.5& 1.9.t
47.2+0.8? 48.1+0.9?
-14.4k1.7 -1l.lk1.6
Values are means + SE of 9 young and 10 middle-aged subjects at rest and exhaustion at 30 and 10°C ambient temperatures. sodium; K+, plasma potassium; Hct, hematocrit; % APV, percent change in plasma volume; %PCV, percent packed cell volume. rest: * P < 0.05, “f P < 0.02. Middle-aged vs. young: $ P < 0.05, Q P < 0.01. There was no difference between conditions.
thetic nervous system. This increase was probably responsible for the cutaneous vasoconstriction. The plasma levels of the other hormones we studied were unaffected by the cold temperature, possibly because of the short time of exposure. Exhaustive exercise caused an increase in all plasma hormone concentrations measured under both ambient conditions. At the temperate ambient temperature, the magnitude of hormonal response is consistent with other studies using exercises of similar duration and intensity (9,24,26). In our study, this response was not influenced by aging. In particular, the ANF response was not significantly different in Y and MA subjects. Recently, Freund et al. (10) found a higher ANF plasma concentration in MA than in Y athletes during a marathon, after 10 km of running. The proposed mechanism is an exaggerated response to central blood volume expansion in older subjects. Differences in type, intensity, and duration of exercise may explain the discrepancy observed between the studies. Furthermore, Freund et al. reported higher resting blood pressure values in the MA than in the Y subjects, whereas no difference in resting blood pressure was found in our populations. Perhaps differences in blood L
Na+, plasma Exhaustion vs.
pressure, and presumably central volume responses, contribute to the difference between studies. Moderate cold exposure induced a further increase in the plasma NOR concentration obtained at exhaustion. This result is in agreement with the higher plasma catecholamine level previously observed when exercise was performed in cold air (1, 32). This further rise probably has a role in particular cardiovascular adjustments generally observed under this condition. Thus, for a given exercise intensity, the blood pressure is higher; the cardiac output is not influenced by cold exposure but is obtained by a lower HR and a greater systolic volume (3, 8, 31). Exhaustion
Rest
l
+
I
P
1
7n
YO"W middle-aged l
A
Young I middle-aged
hyper-reactive
moderately
reactive
FIG.
30°C
3. Individual differences (means + SE) between for all submaximal exercise intensities.
SBP at 10 and
FIG. 4. Epinephrine (EPI) and norepinephrine (NOR) plasma centrations at rest and exhaustion in Y (n = 8) and MA (n = 10) at 30 and 10°C ambient temperatures. Values are means t SE. 0.05, exhaustion vs. rest; .P< 0.05,10vs.30°C;oP
