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J Appl Physiol 89: 621-628, 2000;
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Vol. 89, Issue 2, 621-628, August 2000

Does gender influence human cardiovascular and renal responses to water immersion?

Donald E. Watenpaugh1, Bettina Pump1, Peter Bie2, and Peter Norsk1

1 Danish Aerospace Medical Centre of Research, National University Hospital, DK-2200 Copenhagen; and 2 Department of Physiology, University of Odense, DK-5000 Odense, Denmark


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

We hypothesized that women and men exhibit similar cardiovascular and renal responses to thermoneutral water immersion (WI) to the neck. Ten women and nine men underwent two sessions in random order: 1) seated nonimmersed for 5.5 h (control) and 2) WI for 3 h, with subjects seated nonimmersed for 1.5 h pre- and 1 h postimmersion. We measured left atrial diameter, heart rate, arterial pressure, urine volume and osmolality, and urinary endothelin, urodilatin, sodium, and potassium excretion. No significant difference existed between groups in cardiovascular responses. The groups also exhibited mostly similar renal responses to immersion after adjustment for body mass. However, female urodilatin excretion per kilogram during immersion was over twofold that of men, and the female kaliuretic response to immersion was delayed and less pronounced relative to that in men. Men may excrete more potassium than women during immersion because men possess greater lean body mass (potassium per kilogram). Results obtained in men during WI may be cautiously extrapolated to women, yet urodilatin and potassium responses exhibit gender differences.

sex; hemodynamics; endothelin; urodilatin; diuresis; natriuresis; kaliuresis


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

HUMANS USE WATER IMMERSION (WI) for relaxation/recreation, as a medical therapy, and as a research tool for studying cardiovascular physiology and fluid and electrolyte metabolism (4, 8, 16, 23). WI induces an increase in central blood volume by redistributing venous blood and extracellular fluid from the lower to the upper part of the body. The heart and central circulation are distended, leading to stimulation of volume and pressure receptors, which in turn leads to a diuresis through neural and endocrine pathways.

As in many other areas of human physiology, investigators have performed most WI research only in male subjects, for a variety of reasons. One reason commonly given is to avoid effects of the female menstrual cycle on a study. Men and women, however, may respond differently to stimuli such as immersion, such that research performed on male subjects may not accurately represent female responses. On average, men are taller and heavier than women, so obvious differences in physiology exist simply due to size. For example, men probably excrete more urine than women in response to WI simply because men are larger on average. However, many size-independent differences also exist. For example, male lower body negative pressure (LBNP; simulated orthostasis) tolerance exceeds that of women (13, 29), and women display greater heart rate elevation than men at 50 mmHg LBNP, which approximates the orthostatic stress of standing (29). WI compromises responses to orthostatic type stress (13). Therefore, one might expect women to experience greater alterations than men in responses to orthostasis after WI.

Only one prior study exists that compared women and men using WI: Hordinsky and colleagues (13) investigated responses to LBNP in each group before and after 6 h of WI vs. 6 h of bed rest. They found that, although the two genders exhibited similar reduction of LBNP tolerance (21%) after WI, women experienced preferentially greater reduction of tolerance (21%) than men (6%) after bed rest. They did not report detailed, gender-specific responses to the immersion per se. Our investigation compared cardiovascular and renal responses of women and men to acute (3-h) thermoneutral WI to the neck using noninvasive techniques. We hypothesized that women and men exhibit similar responses to WI after adjustment of renal responses per kilogram body mass. We also compared gender responses to standing (orthostasis) before and after WI. We expected that women may exhibit greater post-WI heart rate elevation than men.


    METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Subjects. Nine male and ten female healthy subjects participated in this study, which was approved by the Ethics Committee of Copenhagen [no. (KF) 01-238/96]. All subjects provided written consent for their participation after they were fully informed about the study. Subjects' health status was determined from their medical history and urinalysis, and they were screened for echocardiographic (left atrial) image quality. No subject used tobacco or medications, including oral contraceptives. The two groups exhibited the following characteristics: female age range, 20-27 yr; height, 170 ± 7 cm (mean ± SD); mass, 61.5 ± 5.9 kg; male age range, 19-28 yr; height, 183 ± 4 cm; mass, 78.4 ± 8.0 kg. Men averaged 8% taller and 27% heavier than women (P < 0.001).

Protocol. Subjects underwent two experimental sessions in balanced random order: 1) seated nonimmersed in a chair for 5.5 h as a time control for immersion and 2) seated WI to the level of the sternoclavicular notch (neck) for 3 h. Subjects sat nonimmersed in a chair for a 1.5-h preimmersion baseline period before WI and a 1-h recovery period after WI. In addition, subjects stood quietly for 5 min just before and after immersion and correspondingly at the 1.5- and 4.5-h time points of the time-control session. Control and WI sessions were separated by at least 6 days.

Female subjects underwent control and immersion sessions during the same phase of their menstrual cycle such that the two sessions occurred ~1 mo apart. Subjects reported their cycle length and date of onset of their last menses. All female subjects reported having regular menstrual cycles of reliable length. We scheduled studies to avoid menses and midcycle by at least 2 days. The second study was scheduled as close as possible to one menstrual cycle length after the first. For hygienic reasons, female subjects were not studied during menses. Four women participated during the follicular phase of their menstrual cycle, and the other six participated during the luteal phase. This participation of subjects in the two longest phases thereby represented female responses during the majority of the menstrual cycle.

For 3 days before each participation, subjects consumed a diet containing 2.0 mmol sodium · kg body mass-1 · day-1, with water ad libitum. Subjects were instructed to avoid caffeine, alcohol, and strenuous exercise for those 3 days. All urine was collected for 24 h before a study to determine 24-h sodium excretion and thus assess whether the diet had achieved sodium balance. Twenty-four-hour sodium output before experiments (2.0 ± 0.1 mmol sodium · kg body mass-1 · day-1) equaled input and did not differ significantly between groups or study conditions (control vs. immersion).

At 7:00 AM on the morning of a study, subjects ate a light breakfast of two Wasa crackers with jam, with water only as necessary to consume the crackers (~100 ml). No other food or drink was consumed after 8:00 PM of the evening before the study. Subjects wore a bathing suit for both immersion and seated-control studies. The subjects reported to the laboratory just before 8:00 AM on the morning of the study. They emptied their bladders to complete the 24-h urine collection, and they were weighed to ±0.1 kg (scale). They then drank 6.0 ml of tap water/kg body mass (~350-400 ml). The subjects then sat upright in a chair outside the immersion tank. At 30 min and at 1 h later, left atrial diameter, arterial blood pressure, and heart rate were measured. At 1.3 h after being seated, subjects emptied their bladders into a bedpan while remaining seated and then drank 3.0 ml tap water/kg body mass (175-200 ml).

The subjects then stood for 5 min, and heart rate and blood pressure were measured after the fifth minute of standing. Subjects stood quietly with their feet comfortably apart and with approximately equal weight on each foot. The purpose of the stand tests was to assess whether women experience relatively greater WI-induced elevation of standing heart rate than men.

After the standing measurements, the subjects began WI or continued the time-control sitting period. Subjects were immersed in a plastic tank (0.6 × 1.6 × 1.6 m) equipped with a chair that could be lowered into or lifted out of the tank with a vertical hoist. Hemodynamic measurements during immersion (left atrial diameter, arterial blood pressure, and heart rate) occurred at 0.5-, 1.5-, and 2.5-h time points. At 1-, 2-, and 3-h (end-immersion) time points, the subjects voided their bladders while remaining seated and subsequently drank 3.0 ml tap water/kg body mass. To empty the bladder during the immersion period, the subjects were temporarily hoisted from the tank, and they dried off with a towel as necessary to avoid contaminating their urine samples with immersion tank water.

Immediately after the final immersion measurements, the subjects exited the immersion tank and dried briefly with a towel as a precaution against becoming chilled. They then stood quietly for 5 min as before immersion. Heart rate and blood pressure were measured after the fifth minute of standing, as before. Thereafter, the subjects sat upright in a chair outside the immersion tank. Seated hemodynamic measurements were performed at 0.5 and 1 h after immersion. The subjects then emptied their bladders a final time. Poststudy body mass was measured in a dry bathing suit, and subjects were then discharged. During the seated-control study, the timing of measurements was identical to that described above for immersion studies.

Experimental conditions. Immersion water temperature averaged 34.6 ± 0.1°C (mean ± SD), room air temperature averaged 26.8 ± 0.3°C, and relative humidity averaged 49 ± 9%. Conditions were identical between groups and sessions. Subjects were allowed to watch television or read during experiments. In most cases, two subjects of the same gender were studied concurrently (one control, one immersed), with their study schedules staggered a few minutes to avoid interference between their measurements.

Measurements. Left atrial diameter was measured with echocardiography (Aloka SSD 500, Tokyo, Japan). The left atrium was imaged in the parasternal long-axis view, and an M-mode transect was positioned through the aortic valve (6). Left atrial diameter was measured at end-expiration as an average from at least 3 m-mode printouts. The M-mode images were analyzed after completion of the experiment, with the analyzer blinded to experimental treatment. Left atrial diameter coefficient of variation averaged 3% across the 5.5-h seated time-control period in this study (n = 19). Johansen and co-workers (14) demonstrated that WI-induced elevation of parasternal long-axis left atrial diameter agrees well with elevation assessed via the apical four-chamber echocardiographic view. They also found that left atrial diameter elevation parallels central venous pressure elevation during WI.

Arm arterial blood pressure was measured at heart level by conventional auscultation. A natural tendency exists for the arm to float above heart level during blood pressure measurement in WI to the neck, due to the buoyancy of the inflated cuff. This arm flotation artifactually decreases measured blood pressure because of a decrease in brachial arterial gravitational blood pressure (24). Therefore, care was taken to hold the arm under water at heart level during WI blood pressure measurement. Pulse pressure equaled systolic arterial pressure minus diastolic arterial pressure, and mean arterial pressure was calculated as diastolic pressure plus one-third of pulse pressure. Heart rate was measured from the radial arterial pulse counted over 1 min.

Urine volume was measured with graduated cylinders. Urine osmolality was measured by freezing-point depression (microosmometer model 3MO plus, Advanced Instruments, Needham Heights, MA). Urine sodium and potassium concentrations were measured with an automated ion-specific probe system (KNA2 sodium-potassium analyzer, Radiometer, Copenhagen, Denmark). The osmometer and sodium-potassium analyzer were calibrated before and after each experiment.

Urine endothelin (27) and urodilatin (1) concentrations were measured with RIA after extraction of urine samples, as previously reported. For endothelin, the assay detection limit equaled 0.3 fmol/ml urine, and percent recovery averaged 92%. For urodilatin, the assay detection limit equaled 0.1 fmol/ml, and percent recovery averaged 82%. To facilitate gender comparisons, we report endothelin and urodilatin excretion rates divided by body mass in kilograms.

Statistics. Multifactor ANOVA, least significant difference post hoc tests, and unpaired two-tailed t-tests assessed gender effects on cardiovascular and renal dependent variables. Repeated-measures ANOVA followed by least significant difference post hoc tests assessed within-gender time and immersion effects on dependent variables. Paired t-tests also evaluated within-gender effects where appropriate. Tests were performed at a significance level of 0.05 by Statgraphics Plus for Windows software (version 2.0, Manugistics, Rockville, MD). Results are expressed as means ± SE.


    RESULTS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Cardiovascular responses. WI increased left atrial diameter in both women (28%) and men (25%): no significant gender difference existed in left atrial diameter or the WI-induced increase in left atrial diameter (Table 1). Heart rate decreased significantly during WI in both women (21%) and men (16%; both P < 0.05; Fig. 1). No significant gender difference appeared in heart rate or its response to immersion (P = 0.25), yet, at the initial immersion time point, female heart rate had already decreased significantly (P < 0.05), whereas male heart rate had not. Neither left atrial diameter nor heart rate changed significantly during seated-control conditions.

                              
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  		Table 1.   Left atrial diameter and arterial blood pressure responses to water immersion in women and men



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  		Fig. 1.   Female and male heart rate responses to seated-control and thermoneutral water immersion (WI) conditions. Some error bars are omitted for clarity. On average, WI decreased female heart rate 21% and male heart rate 16% relative to baseline (pre) conditions (no significant gender difference). post, After the end of WI. * Less than baseline (pre-WI) mean, P < 0.05.

Male mean arterial pressures exceeded female pressures by ~8-12 mmHg at all times in all experimental conditions (P < 0.05; Table 1). At the second and third hours of immersion, systolic arterial pressure increased significantly from preimmersion levels similarly in both groups (~10-12 mmHg, 10%; P < 0.05), and female systolic pressure exceeded the corresponding seated time-control value at the third hour of immersion (P < 0.05). Neither diastolic arterial pressure nor mean arterial pressure changed significantly during immersion. Arterial pulse pressure increased in both groups at the second and third hour of immersion relative to preimmersion levels (P < 0.05) but not relative to corresponding seated-control levels. No significant changes in arterial blood pressures occurred during seated-control conditions.

Neither group exhibited significantly altered responses to 5 min of standing after 3 h of WI. As with seated measurements, overall male arterial blood pressures exceeded those of women on average, but no other gender differences appeared in the standing-test results (Table 2). Because no gender differences appeared, we pooled female and male data and performed statistical analyses on the pooled data to see whether any effects of immersion on standing emerged. Pooled data indicated that standing heart rate after 4.5 h of the seated-control period (74 ± 4 beats/min) decreased 8% relative to heart rate at the earlier (1.5 h) standing time point of the seated-control period (80 ± 4 beats/min; n = 19, P = 0.023). No such decrease in standing heart rate occurred after WI (preimmersion standing heart rate, 78 ± 3 beats/min; postimmersion, 79 ± 3 beats/min). Standing mean arterial pressure after immersion was 3% less than that before immersion (preimmersion, 91 ± 2 mmHg; postimmersion, 89 ± 2 mmHg; n = 19, P = 0.029). No significant reduction of standing mean arterial pressures occurred after the seated-control period in the pooled data.

                              
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  		Table 2.   Female and male responses to 5 min of standing before and after 3 h of water immersion

Renal responses. In women, endothelin excretion per kilogram body mass did not differ significantly from baseline (pre-WI) in either immersion or seated-control conditions (Table 3). However, immersion values significantly exceeded corresponding seated time-control values at the third hour of immersion (P < 0.05). In men, endothelin excretion per kilogram body mass increased significantly from baseline during the first hour of seated-control and immersion conditions (P < 0.05). Thereafter, in men, endothelin excretion remained significantly elevated relative to baseline at 2 h of immersion and increased sharply during the hour postimmersion (significantly exceeding baseline and seated time-control values).

                              
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  		Table 3.   Endothelin responses to water immersion in women and men

Women and men exhibited significantly different urodilatin excretion responses to WI (Fig. 2). In women, urodilatin excretion per kilogram body mass increased 63% from baseline during the first hour of immersion (P < 0.05); this increase also significantly exceeded corresponding time-control and male-immersion levels (P < 0.05). At the second and third hour of immersion, female urodilatin excretion was greater than time-control (P < 0.05) but not baseline (pre-WI) levels. Male urodilatin excretion per kilogram body mass did not change significantly from baseline levels for either condition, although a consistent trend appeared for immersion values to exceed seated-control values (Fig. 2). To further examine this trend, we calculated and compared male cumulative urodilatin excretion during the 3-h immersion period with cumulative excretion during the corresponding time control period. With this analysis, male urodilatin excretion per kilogram over the 3-h immersion period was 96% greater than excretion over the corresponding 3-h seated-control period (P = 0.039).


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  		Fig. 2.   Female and male urodilatin excretion per kilogram before, during, and after seated-control and thermoneutral WI conditions. Some error bars are omitted for clarity. * Greater than baseline (pre-WI) mean, P < 0.05; # WI mean > seated-control mean, P < 0.05; § female WI mean > corresponding male WI mean, P < 0.05.

To further explore the difference between genders in urodilatin response to immersion, we compared cumulative urodilatin excretion per kilogram during immersion for the two groups. For this comparison to best assess effects of immersion per se, we calculated and subtracted seated-control cumulative urodilatin excretion from the cumulative immersion data for each group. We found that female cumulative urodilatin excretion over the 3-h immersion period was 128% greater than male cumulative excretion (P = 0.046).

WI increased urine production rate (V) in both groups relative to preimmersion and seated-control levels, significantly more so in men than women. After adjustment of V for kg body mass, gender differences in response to immersion disappeared: the two groups produced similar peak volume excretion of 10.9-11.0 ml · min-1 · kg-1 during the second hour of immersion (3.5- to 4.5-fold greater than baseline, P < 0.05; Fig. 3). Both groups also showed small but significant increases in V per kilogram during the seated-control period (P < 0.05). The only gender difference in V per kilogram results appeared postimmersion: women exhibited significantly reduced V per kilogram relative to both seated-control levels and male postimmersion levels (P < 0.05).


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  		Fig. 3.   Female and male urine flow rate per kilogram body mass (V per kg) before, during, and after seated-control and thermoneutral WI conditions. Some error bars are omitted for clarity. * Greater than baseline (pre-WI) mean, P < 0.05; # WI mean different from corresponding seated-control mean, P < 0.05; § female post-WI mean < corresponding male post-WI mean, P < 0.05.

WI led to similar net fluid loss in both groups, as assessed by body mass measurement before and after immersion. Women lost 0.4 ± 0.1 kg during immersion, and men lost 0.5 ± 0.1 kg (both P < 0.05). No significant change in body mass occurred during seated-control conditions (women, 0.0 ± 0.1 kg; men, 0.1 ± 0.1 kg).

Male urinary sodium excretion rate (UNaV) responses significantly exceeded female responses before adjustment for body mass but not after (P < 0.05). UNaV and UNaV per kilogram body mass (Fig. 4) each increased progressively during the 3-h immersion in both groups. During the third hour of immersion, sodium excretion responses peaked at 2.6-2.9 µmol · min-1 · kg-1, which constituted 3- to 3.5-fold increases from baseline levels (P < 0.05). Sodium excretion did not vary significantly during seated-control conditions. Postimmersion UNaV per kilogram did not differ significantly from baseline.


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  		Fig. 4.   Female and male sodium excretion per kilogram body mass (UNaV per kg) before, during, and after seated-control and thermoneutral WI conditions. Some error bars are omitted for clarity. * Greater than baseline (pre-WI) mean, P < 0.05; # WI mean > corresponding seated-control mean, P < 0.05.

Potassium excretion rate (UKV) responses to immersion showed significant gender differences. Male UKV and UKV per kilogram increased significantly from baseline by 1 h of immersion (P < 0.05), whereas female levels did not yet significantly exceed baseline at that time. Male UKV per kilogram significantly exceeded female levels at 3 h of immersion (P < 0.05) and tended to be greater at other immersion and postimmersion time points (Fig. 5). In seated-control conditions, UKV per kilogram increased from baseline in men (P < 0.05) but not in women. Variation in male cumulative UKV significantly exceeded female variation (F-test of variances, P = 0.012). As with urodilatin (see above), we further examined the difference between genders in UKV per kilogram responses to immersion by comparing cumulative potassium excretion during the 3-h immersion for the two groups (t-test assuming unequal variances) with borderline results (P = 0.064).


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  		Fig. 5.   Female and male potassium excretion per kilogram body mass (UKV) before, during, and after seated-control and thermoneutral WI conditions. Some error bars are omitted for clarity. * Greater than baseline (pre-WI) mean, P < 0.05; # WI mean > corresponding seated-control mean, P < 0.05; § male WI mean > corresponding female WI mean, P < 0.05.

Urine osmotic excretion (UosmV) per kilogram responses to immersion closely matched UNaV per kilogram responses and showed no significant gender differences. Both groups increased UosmV during the last 2 h of immersion relative to both baseline and seated-control conditions (P < 0.05). Male UosmV increased from baseline during seated-control conditions (P < 0.05), yet female values did not.

We did not statistically compare responses of women studied during the follicular vs. luteal phases of the menstrual cycle due to the small sample sizes (particularly follicular phase, n = 4), yet we did observe trends for V per kilogram, UKV per kilogram, and UosmV per kilogram during the follicular phase to exceed those during the luteal phase. For example, the grand mean of UKV per kilogram from follicular phase subjects was 28% greater than that from luteal phase subjects. Also, cumulative UKV per kilogram during WI averaged 74% greater than seated time-control levels in follicular phase subjects and 65% greater than control levels in luteal phase subjects. Regarding urodilatin excretion per kilogram, the grand mean from follicular phase subjects was 10% less than that of the luteal phase subjects. The two groups exhibited similar elevation of cumulative urodilatin excretion during WI relative to time-control excretion (follicular, 121%; luteal, 123%).


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

This work is the first to compare women and men in terms of their cardiovascular and renal responses to acute thermoneutral WI. As expected, our results collectively indicate that women and men exhibit largely similar responses to acute thermoneutral WI to neck level. However, we observed significant quantitative differences between the women and men in their urodilatin and potassium responses to immersion: women excrete more urodilatin per kilogram body mass and less potassium than men.

Similarities between this study and prior literature on men. Male responses to immersion in this study agree with those from previous similar studies (5, 18, 22). For example, Larsen and co-workers (18) reported an ~9 beat/min reduction in men's heart rate at 1.5 h of a 3-h thermoneutral immersion to the neck relative to seated-control levels, compared with an 11 beats/min reduction in the present study. Both studies reported increased arterial pulse pressure during immersion (~10 mmHg, or 24%) with no change in mean arterial pressure. Larsen and colleagues found ~4.0-fold increases in male V averaged over 3 h of immersion, ~3.3-fold increases in UNaV, and ~2.7-fold elevation of UKV; all responses approximate male results from the present work (V, 3.1-fold elevation; UNaV, 2.7-fold elevation; UKV, 2.6-fold elevation). On the basis of these similarities with prior literature and the present gender similarities, we conclude that women and men respond similarly to WI for most of the variables we measured, with the exceptions discussed below.

Gender differences in urodilatin responses to immersion. Women excreted over two times as much urodilatin per kilogram body mass as men during WI. The gender difference in urodilatin excretion became statistically insignificant within the 3-h WI period, suggesting that it is a transient observation during early WI that may not be sustained during longer WI periods. Estrogen may play some role in explaining relatively greater female urodilatin excretion during WI. For example, Seeger and colleagues (28) demonstrated that transdermal estradiol significantly increased urodilatin excretion in postmenopausal women.

Urodilatin elicits diuresis, natriuresis, and cardiovascular effects in humans (1, 15, 20). Therefore, it is interesting that men and women exhibited similar diuretic, natriuretic, and cardiovascular responses to WI in the present study, despite the substantially greater urodilatin excretion in women. This observation implies that, if urodilatin influences renal function, urodilatin acts less strongly in women than in men and/or that other factors in women compensate for effects of their relatively elevated urodilatin response to immersion. One such factor may be arterial blood pressure. Women had lower blood pressure than men in our study, which would contribute to reduced pressure-mediated renal responses such as diuresis and natriuresis. From another view, the greater female urodilatin response may compensate for the reduced renal effects of blood pressure during WI relative to men.

Male urodilatin data from the present study agree with male data from a prior WI study conducted in similar experimental conditions: Norsk and colleagues (25) observed ~100% greater urodilatin excretion during 3 h of immersion than during the seated-control period. In the present study, male cumulative urodilatin excretion over the 3-h immersion period was 96% greater than over the corresponding 3-h seated-control period. The two studies employed different urodilatin RIAs, which reinforces their agreement. Using the same urodilatin antibody as Norsk and co-workers (25), Nakamitsu and colleagues (22) also noted a significant increase (~60%) in male urodilatin excretion during WI relative to seated-control conditions. That assay yields substantially higher baseline urodilatin levels than the assay used in the present study (1), but the immersion-induced changes appear to be similar.

Gender differences in potassium responses to immersion. The male kaliuretic response to WI exceeded that of women, even after accounting for the fact that men weighed more than women in this study. The data suggest that this gender difference might become still more apparent during immersion >3 h. Epstein (4) attributed the kaliuresis of WI to increased fluid delivery to the distal tubules and to ongoing effects of preimmersion aldosterone levels (i.e., latent kaliuretic effects of aldosterone before its immersion-induced reduction). Some evidence exists indicating that women exhibit lower basal aldosterone levels than men (21), yet other results suggest no difference (7). If women in our study had lower aldosterone than men, this might explain women's lesser kaliuretic response to WI. If aldosterone in some way reduces renal urodilatin secretion, then lower female aldosterone levels would help us explain higher female urodilatin, but this is also speculative.

Alternatively, body composition differences may explain gender differences in the kaliuretic response to immersion: on average, male percent lean body mass (~86%) exceeds female percent lean body mass (~75%; Ref. 19). Adipose tissue contains less intracellular water, and therefore potassium, than lean tissue (2). Part of the kaliuretic response to WI comes indirectly from the intracellular fluid compartment (9, 17). Therefore, men may excrete more potassium than women in response to immersion because they contain more intracellular fluid and potassium per kilogram than women. However, we did not quantify lean body mass or fitness level in the present study, so this explanation remains tentative.

Did the relatively greater urodilatin response in women possibly blunt their WI-induced kaliuresis? Bestle and co-workers (1) demonstrated that exogenous urodilatin reduces potassium excretion, which supports this scenario. However, the timing of responses we saw opposes this idea: the statistically significant urodilatin gender difference was maximal during the first hour of WI, whereas the significant potassium difference occurred during the third hour. On the other hand, if potential urodilatin actions on potassium excretion involve substantial time delay (e.g., for protein synthesis), some relationship between them may yet exist.

Exogenous urodilatin decreases aldosterone in humans (1), and aldosterone mediates kaliuresis. However, it is unlikely that urodilatin reduced kaliuresis in women via this mechanism, because urodilatin is considered a paracrine substance in the kidney (1, 15, 20). Endogenous urodilatin spillover from the kidney to the systemic circulation appears to be too low to lead to measurable plasma levels (1, 3). Therefore, urodilatin is unlikely to influence plasma levels of aldosterone.

Other observations. No indication of gender differences appears in urinary endothelin responses to immersion. In both groups, an inconsistent pattern emerged for urinary endothelin excretion to increase during and after immersion relative to seated-control levels. Gulberg and Gerbes (10) saw a small but similar trend toward elevation of plasma endothelin levels after 1 h of head-out WI relative to prior sitting values. One might predict reduced endothelin levels during immersion, because the vasodilation commonly associated with immersion (16) is incompatible with endothelin's actions as a vasoconstrictor (26). Nevertheless, we found some evidence for immersion-induced stimulation of endothelin release.

No gender differences appeared in cardiovascular responses to pre- vs. postimmersion stand tests, and no effects of WI on responses to standing occurred within either group. Pooled stand-test results indicate that 3 h of sitting with no immersion reduces the heart rate response to subsequent standing, yet no such reduction follows 3 h of WI. Therefore, cardiovascular compensation for the orthostatic stress of prolonged sitting appears to attenuate the heart rate response necessary for subsequent standing. Given the 21% reduction of LBNP tolerance found by Hordinsky and co-workers (13) after 6 h of WI, our findings suggest, not surprisingly, that a 3-h WI does not alter orthostatic responses nearly as much as a 6-h WI.

For many variables, data from the women exhibited less variability than data from the men. For example, standard errors of female UNaV and UKV during immersion equaled less than half of the corresponding male standard errors (see Figs. 3-5). Residual bladder volume may contribute to higher male variability. Because of their less complicated urinary tract, women may empty their bladders more completely than men and therefore have less residual volume than men (11). Reduced data variability may provide an advantage for using female subjects in studies of renal function.

Limitations of this investigation. We used only noninvasive methods in the present study, so several variables involved in the human response to WI, such as plasma hormone levels and key cardiovascular pressures (e.g., central venous pressure), were not measured. This limitation prevents us from concluding that no gender differences exist in responses of those variables to immersion. In light of the gender differences we observed in urodilatin and potassium excretion, this deficiency of the present study offers possibilities for future work. We employed only young adult subjects (ages 19-28 yr), so our results and conclusions do not necessarily apply to children or to older age groups. Again, we did not quantify body composition or fitness, so we draw no definitive conclusions based on gender differences in those variables.

For a gender comparison to be valid, it should include as much of the biological variability within each gender as possible. To represent female responses during the majority of the menstrual cycle, we intentionally pooled results from women in the follicular and luteal phases of their cycle. In this particular experiment, we did not study women during menses for hygienic reasons, so our study is limited in that the data do not represent female physiology during menses. Although we did observe some trends toward differences between the follicular and luteal groups, examination of effects of menstrual cycle phase on responses to WI is beyond the scope of this article. Ho and co-workers (12) compared responses of young women to 3 h of thermoneutral WI to the neck during follicular vs. luteal phases. They measured urinary norepinephrine, dopamine, and sodium excretion and serum sodium transport inhibitor, and they reported no significant phase differences. It remains possible that menstrual cycle phase influences WI responses for other variables.

Conclusions. The present results largely confirm our expectations: no significant gender differences exist in left atrial diameter, heart rate, arterial pressure, endothelin, V per kilogram, UNaV per kilogram, or UosmV per kilogram responses to thermoneutral WI to the neck. With partial confirmation of our hypothesis, previous and future findings in male subjects during WI may to some extent be extrapolated to women. However, this conclusion does not apply to male data concerning potassium or urodilatin physiology: in response to immersion, men excrete less urodilatin per kilogram and more potassium than women. Previous studies concerning potassium or urodilatin performed in male subjects require repetition in female subjects, and new studies may be necessary to define mechanisms and implications of observed gender differences.


    ACKNOWLEDGEMENTS

The authors heartily thank the subjects for their participation; Trine Eidsvold, Mette Hammerum, Dorte Hansen, Mikkel Jensen, Birthe Lynderup, Anders Madsen, Anders Pedersen, Inge Pedersen, Lotte Rosenkrands, Line Soot, and Kresten Yvind for excellent technical support; and Drs. Anders Gabrielsen and Lars Bo Johansen for helpful discussions.


    FOOTNOTES

D. Watenpaugh was a guest scientist at the Danish Aerospace Medical Centre of Research during the conduct of this study.

This study was supported by Danish Research Councils Grant 9602455.

Address for reprint requests and other correspondence: D. Watenpaugh, Dept. of Integrative Physiology, Univ. of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, Texas 76107 (E-mail: dwatenpa{at}hsc.unt.edu).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Received 2 November 1999; accepted in final form 31 March 2000.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

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J APPL PHYSIOL 89(2):621-628
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