European Journal of

Applied

Eur. J. Appl. Physiol. 41, 41-50 (1979)

Physiology and Occupational Physiology 9 Springer Verlag 1979

Plasma Aldosterone, Renin Activity, and Cortisol Responses to Heat Exposure in Sodium Depleted and Repleted Subjects M. Follenius, G. Brandenberger, B. Reinhardt, and M. Simeoni Centre d'Etudes Bioclimatiques, 21, rue Becquerel, F-67087 Strasbourg Cedex, France

The effect of 90-min heat exposure (46 ~ C, 35 mbar) on plasma aldosterone (PA) patterns was studied and the respective roles of plasma renin activity (PRA), adrenocorticotropin (ACTH), Na + and K + concentrations in the control of PA response were investigated in eight subjects on a low sodium diet and in five subjects on a high sodium diet. In all subjects, transitory PA increases of varying importance were observed, which were not related to sweat losses (less than 1% bodyweight) or to rectal temperature rise. In sodium-repleted subjects, basal PA and PRA levels as well as heat-induced rises were low (mean PA peak level = 12.62 _+ 1.15 ng/100 ml). They were enhanced by sodium depletion and PA reached a mean peak level of 34.07 + 2.73 ng/100 ml. But, in both conditions, the heat-induced PA peaks were 3-times higher than the initial levels. PA correlated with PRA in all but one of the sodium-repleted subjects and in 6 of the 8 sodium-depleted subjects. A C T H release, as measured by plasma cortisol (PC) levels, occurred in those subjects who noted an increased feeling of annoyance and discomfort. Thus, PA correlated positively with PC in 4 sodium-depleted subjects. A high sodium intake improved heattolerance. Plasma K + and N a + concentrations were not significantly modified by exposure to heat. PA increases can occur without concomitant changes in PRA, PC, K + or Na +, which suggests that an additional factor may play a role in aldosterone regulation during acute heat exposure. Summary.

K e y w o r d s : Aldosterone regulation - Plasma electrolytes - Rectal temperature - Sweat loss

Adrenal hormones are generally admitted to be involved in man's thermoregulatory responses to heat exposure. Increased excretions of urinary metabolites (Beisel et al., 1968; Fletscher et al., 1961; Smiles and Robinson, 1971; Streeten et al., 1960) and increased plasma concentrations of cortisol (Collins et al., 1969) and aldosterone Offprint requests to: M. Follenius, M.D. (address see above)

0301-5548/79/0041/0041/$ 02.00

42

M. Follenius et al.

(Kosunen et al., 1976) have been found in m a n exposed to high environmental temperatures. It is k n o w n that under normal climatic conditions, aldosterone biosynthesis is controlled by the renin-angiotensin system, the pituitary secretion of adrenocorticotropin ( A C T H ) and the plasma levels of N a + and K +. The renin-angiotensin system has been considered to play a major role, but recent reports have challenged its primacy in regulating aldosterone secretion, suggesting interaction of the above mentioned stimuli (Hata et al., 1976; H i m a t h o n g k a m et al., 1975; Kern et al., 1975). However, no studies on the respective roles of the four k n o w n regulatory factors during passive heat exposure have yet been reported. This study assesses the effect of high environmental temperature on the day-time pattern of plasma aldosterone (PA), renin activity (PRA), cortisol (PC), and electrolytes (Na 4 and K +) by measuring their concentrations at short intervals. A n attempt was made to determine temporal relationships between the various stimuli and aldosterone secretion in m a n at different levels of P R A induced by changes in dietary sodium intake.

Methods Healthy volunteers (20-28 years) were studied in two randomized experimental series at about onemonth intervals. All experimentswere conducted between 0800 h and 1500 h. During control periods, the climatic chamber was kept at a constant temperature (28~ C) and humidity (pH20 = 14 mbar). On heat exposure days, the temperature and humidity were suddenly raised to 46~ C and 35 mbar. The heat exposure lasted 90 rain, from 1000-1130 h. The subjects rested in an armchair and standard meals were served at 0815 h (3700 kJ) and 1215 h (4600 kJ). Ad libitum water intake was allowed after the exposure period. In a first experimental series, ten subjects were placed on a low sodium diet of 20--30 mEq of Na+/day. In a second experimental series, five of them received a high sodium diet of 200 mEq of Na+/day. Both groups were on a constant dietary intake of 100 mEq K+/day. When the subjects had achieved metabolic balance as judged by their urinary sodium-potassiumexcretion (3-5 days), the experimentwas carried out. A small plastic catheter was inserted into an antecubital vein and blood samples were collected from 800-1500 h at 10-rain or 20-min intervals removing a total blood volume of 250 ml. Heart rate, rectal temperature, and body weight losses were recorded. Subjective ratings were obtained by the use of questionnaires. Plasma aldosterone concentration was measured with a radioimmunoassay method developed in this laboratory and based on the method of Gianotti et al. (1974). The aldosterone antiserum was prepared against a bovine serum albumin conjugate of aldosterone-3-carboxymethyl-oxime-18-21diacetate. Plasma cortisol concentration was measured with the competitive protein binding method of Murphy (1967) with the modifications described by Leclerq et al. (1967). Plasma renin activity was measured by radioimmunoassay of angiotensin-I generated after incubation of plasma (Haber et al., 1969). Na + and K + in plasma and urine were measured by flame photometry. Plasma protein was measured by the method of Weichselbaum (1946). Changes in plasma volume were calculated from changes in hemoglobin and hematoerit (Dill and Costill, 1974) The t-test was used to assess the statistical significanceof differences in plasma levels between the experimental days. Correlation coefficients betveen the plasma aldosterone levels and renin activity, cortisol, sodium and potassium levels were computed for each suject.

Results

General Physiological Responses The increases in rectal temperature during heat exposure ranged from 0 . 5 - 0 . 9 ~ C as shown in Table 1. These increases were similar in the same individual in both low

Aldosterone Response to Heat Exposure

43

Table 1. Body-temperature increases and body-weight decreases during heat exposure in subjects on the low and the high sodium diet Subject No.

Low sodium diet

High sodium diet

Temperature increase (~

Body-weight decrease (g)

Temperature increase (~

Body-weight decrease (g)

1

0.6 (37.8-37.2)

512

0.5 (37.5-37.0)

462

2

0.6 (37.4-36.8)

431

0.6 (37.6-37.0)

413

3

0.6 (37.4--36.8)

468

0.7 (37.6-36.9)

527

4

0.7 (37.7-37.0)

534

0.7 (37.6-36.9)

536

5

0.6 (37.7-37.1) 0.6 (37.7-37.1)

568

0.8 (37.6-36.8)

486

6

440

7

0.9 (37.2-36.3)

523

8

0.6 (37.4-36.8)

496

and high sodium intake studies. Body weight losses ranged from 4 1 3 - 5 6 8 g in all subjects and no significant differences were found between subjects on low or high sodium diets. In all subjects, sweat losses were less than 1% body weight. The heart rate increases were about 10--20 beats per min.

Hematocrit N o significant changes were noted in hematocrit during and after heat exposure as compared with pre-exposure levels.

Plasma Proteins After heat exposure, proteins remained at the initial level in subjects on a high sodium diet (7.24 g/100 ml). Values for subjects on a low sodium diet were not significantly different (6.78 g/100 ml at 1000 h and 7.02 g/100 ml at 1130 h).

Plasma Volume The mean decrease in plasma volume, based on changes in hemoglobin and hematocrit, was 5.4 + 1.2% in subjects on a high sodium diet, and 5.2 + 1.1% in subjects

44

M. Follenius et al.

on a low sodium diet. There were no significant differences between the two groups.

Plasma Na + and K + In all subjects, on both high and low sodium diets, plasma Na + and K + concentrations were not significantly modified by exposure to heat. Plasma Na § showed small fluctuations around the mean (138.8 • 0.2 mEq/1 in subjects on a high sodium diet, and 136.8 + 0.2 mEq/1 in subjects on a low sodium diet). Plasma K + tended to increase slightly throughout the experimental day (from 3.97 • 0.05 to 4.15 • 0.06 mEq/1). Mean Na + concentration was significantly lower in the group studied after dietary sodium restriction, whereas mean plasma K + concentrations were not significantly different in the two groups.

Subjective Ratings Some sodium-depleted subjects noted a transitory feeling of discomfort or annoyance during heat exposure, whereas two subjects felt a slight malaise. There was no such trouble in the subjects when on a high sodium diet.

Hormonal Responses Figure 1 depicts the mean responses of PA, PRA, and PC to heat exposure in eight subjects on a low sodium diet and in five of them on a high sodium diet. Two sodium-depleted subjects felt a slight malaise during heat-exposure which considerably modified the hormonal patterns. Their results were discarded from the mean and shown separately in Figure 3. PA and PRA pre-exposure levels were significantly depressed in sodium repletion studies as compared with sodium depletion studies. PC pre-exposure levels did not differ significantly in subjects on both dietary conditions (Fig. 1). In sodium-repleted subjects, mean PA increased in response to heat exposure from 4.06 • 0.70 (SE) to 11.62 + 1.15 ng/100 ml plasma (3-fold) and mean PRA increased from 2.40 + 0.28 to 3.74 + 0.61 ng/ml/h (1.7-fold). Heat exposure did not modify the normal diurnal pattern of PC. A significant positive correlation between PA and PRA levels during the exposure period was found in all subjects but one, whereas PA did not correlate with PC. (Table 2). In the sodium depletion studies, the subjects exhibited large PA increases from 11.14 + 0.74 to 34.07 + 2.73 ng/100 ml (3-fold) with individual peak levels ranging from 17.70 to 43.25 ng/100 ml. PA increases lasted until the end of exposure. Mean PRA levels increased from 3.62 + 0.62 to 5.93 • 0.70 ng/ml/h (1.7-fold). PA correlated positively with PRA in six of eight subjects. PC responses varied widely between individuals. Rises in PC levels occurred in subjects who noted a feeling of discomfort and annoyance. Thus, four sodium-depleted subjects showed significant positive correlations between PC and PA. The individual curves indicate that the

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