1 Deutsche Forschungsansalt für Luft und Raumfahrt-Institute of Aerospace Medicine, 51170 Cologne; and 2 University of Dresden, Department of Nuclear Medicine, 01307 Dresden, Germany
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ABSTRACT |
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A commonly accepted hypothesis is that a chronically high-sodium diet expands extracellular volume and finally reaches a steady state where sodium intake and output are balanced whereas extracellular volume is expanded. However, in a recent study where the main purpose was to investigate the role of natriuretic peptides under day-to-day sodium intake conditions (Heer M, Drummer C, Baisch F, and Gerzer R. Pflügers Arch 425: 390-394, 1993), our laboratory observed increases in plasma volume without any rise in extracellular volume. To scrutinize these results that were observed as a side effect, we performed a controlled, randomized study including 32 healthy male test subjects in a metabolic ward. The NaCl intake ranged from a low level of 50 meq NaCl/day to 200, 400, and 550 meq/day, respectively. Plasma volume dose dependently increased (P < 0.01), being elevated by 315 ± 37 ml in the 550-meq-NaCl-intake group. However, in contrast to the increased plasma volume, comparable to study I, total body water did not increase. In parallel, body mass also did not increase. Mean corpuscular volume of erythrocytes, as an index for intracellular volume, was also unchanged. We conclude from the results of these two independently conducted studies that under the chosen study conditions, in contrast to present opinions, high sodium intake does not induce total body water storage but induces a relative fluid shift from the interstitial into the intravascular space.
total body water; extracellular fluid; plasma volume; metabolic ward; metabolic balances; sodium; nutrient intake
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INTRODUCTION |
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IN HEALTHY ADULTS THE OSMOTIC pressure of body fluids is maintained within a narrow range. Its principal determinant, serum sodium concentration, rarely varies by >2% and generally lies between 135 and 145 meq/l, respectively. This extraordinary constancy is achieved by elevating or lowering total body water to counteract changes in the serum sodium concentration and its anions (21). On the basis of these regulatory mechanisms it is a commonly accepted hypothesis that a high-sodium diet expands not only the intravascular part of extracellular volume but also the total extracellular space (28). One reason for this commonly accepted hypothesis might be that investigations which show a significant sustained body fluid retention due to high sodium consumption have started with subjects sodium depleted (i.e., 2, 14, 18, 22, 24). Sagnella et al. (22) and Singer et al. (24) for example examined among other parameters the body mass change, as an index for changes in total body fluid, in cardiac transplant recipients, patients with essential hypertension, and normal subjects after changes in sodium intake from a sodium-depleted (10 meq sodium/day) state to a consumption of 350 meq sodium/day. They possibly found the significant absolute increase in body mass on the high-sodium diet compared with the low-sodium group due to the onset from a sodium-depleted basis. These results are in line with the above-mentioned common hypothesis. However, as a side effect in a study aimed at the effects of dietary sodium intake on the renal excretion of urodilatin (10), we found no increase in extracellular volume or in total body fluid due to the increased NaCl intake. In contrast to the studies of Sagnella et al. (22) and Singer et al. (24), the test subjects in our study were adapted to a rather average German NaCl-intake level of 220 meq/day (4) and further increased their NaCl intake twice or three times for subsequent 8-day periods. Because these observations were based on an open-study design, we have now performed a controlled randomized study to scrutinize the common hypothesis whether an increase in NaCl consumption leads to total body fluid retention. Four different levels of NaCl consumption, starting from low sodium intake to very high levels of 550 meq/day, were chosen. Body mass and body fluid compartments (plasma volume, intracellular volume) as well as daily metabolic fluid and sodium balances, renal regulatory mechanisms, and fluid- and electrolyte-homeostasis-influencing hormones were determined after the four NaCl-intake levels.
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MATERIALS AND METHODS |
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Both studies were approved by the Freiburg Ethics Committee and the Medical Board of the Deutsche Forschungsansalt für Luft und Raumfahrt (DLR). After written informed consent was obtained, the test subjects stayed for the entire periods in the metabolic ward (Institute of Aerospace Medicine, DLR, Cologne, Germany) to ensure constant environmental temperature of 24°C and humidity of 60%. Physical exercise and alcohol and drug intake were prohibited during the respective study periods.
Study Design
Study I. Six healthy male subjects (age: 24 ± 1 yr; body mass: 76.8 ± 3.8 kg; nonsmokers, nonathletes) participated in a 24-day study. The study consisted of three consecutive 8-day periods, characterized by constant NaCl intake per day, differing from phase to phase. The subjects received 220 meq NaCl/day during the first 8 days, 440 meq NaCl/day during the second phase, and 660 meq NaCl/day during the third phase, respectively.
Study II. Thirty-two (4 randomly assigned groups) healthy male subjects (age: 25.0 ± 0.4 yr; body mass: 74.9 ± 1.0 kg; nonsmokers, nonathletes) participated in a 7-day controlled, randomized study. The four groups differed in their nutritive NaCl content, i.e., 50, 200, 400, and 550 meq/day, respectively.
Diet
Caloric (11.300 MJ/day) and oral water intake (40 ml · kg body massMetabolic Balances
In a preparation study aiming at the sodium loss via sweat, we investigated in three test subjects (mean age 28.7 ± 4.3 yr; mean body wt 76.5 ± 3.1 kg) their sweat sodium loss while on a NaCl-intake level of 50, 200, and 550 meq/day, respectively, for 7 days. The different NaCl-intake periods were at least 3 wk apart to avoid respective dietary impacts. The volunteers were ambulatory on the respective NaCl-intake level for 5 days. On the fifth day they entered the metabolic ward (temperature 24°C and humidity 60%) for analysis of sweat sodium excretion for the following 48 h. The procedure was as follows: the test subject wore an all-body cotton suit, which left just the face open, for 24 h. The cotton suit was washed in deionized water before being worn to exclude sodium contamination from washing powder or tap water. Before the subjects dressed in the cotton suit, they showered with deionized water to wash remaining sodium from the skin. After 24 h they removed the cotton suit, showered using 4 liters of deionized water, and dried themselves with the outer part of the cotton suit. The suit was then washed in a defined volume of deionized water. Both the shower solution and the washing solution were condensed, and sodium concentration was analyzed by flame photometry (Eppendorf FCM 6341). Mean fluid loss via the skin revealed 1,449.79 ± 100.57 ml/day. Mean sweat sodium excretion was 2.88 ± 0.35 meq/24 h with consumption of 50 meq NaCl/day, 3.38 ± 0.28 meq/24 h with consumption of 200 meq NaCl/day, and 4.92 ± 0.28 meq/24 h with consumption of 550 meq/24 h, respectively (ANOVA; P > 0.05). We concluded from these results that sodium loss via sweat under these study conditions is independent from NaCl intake, is very low, and can therefore be neglected for metabolic balance calculations.During studies I and II 24-h metabolic water and sodium
balances were calculated for each day from the respective intake
urinary (studies I and II) (9) and fecal excretion data
(study II). Daily water balances were computed as water intake
(water content of solid food + orally consumed fluid + metabolic water) water output (urinary excretion + evaporative water loss). The
evaporative water loss was determined from weight loss (weight of food
and beverages consumed ± any change in body mass
weight of
urine and feces). Daily sodium balances were calculated according to the following equation: Na+
balance (meq) = Na+
intake (meq/24 h)
[urinary sodium
excretion (meq/24 h) + fecal sodium excretion (meq/24 h)].
Cumulative balances were calculated by summing up 24-h balances.
Body Mass
Body mass was determined during both studies on a sensitive weight scale (±5 g) (Sartorius, type DVM 5703 MP 8-1). The measurement was performed four times each study day after subjects voided at 7 AM, 1 PM, 7 PM, and 11 PM.Body Fluid Compartments
Extracellular volume (study I) was determined by the inulin-dilution method (7). In brief, after a basal blood drawing, 5 g Inutest were applied intravenously. Inulin left the bloodstream and was equally distributed in the extracellular space after 80-100 min. The mixed dye concentration at injection time (t = 0), and thereby the extracellular volume, was determined by backcalculation of the disappearance curve. The disappearance curve for a given test subject was calculated from blood samples before, and 15, 30, 45, 60, 75, and 90 min after injection of inulin. The best-fit curve was then found by linear regression of the semilogarithmic data. The statistical power of this method, when a 10% increase in extracellular volume is expected and six test subjects are examined, is 83%.Mean corpuscular volume (MCV) of erythrocytes, representing changes in the intracellular compartment, was analyzed automatically by using a Coulter Counter (model T660).
Blood volume was calculated by determining the red cell mass with the 51Cr method (17), by correction for the biological half-life of the erythrocytes and isotope and the 1.5% loss of radioactivity of the erythrocytes/day. Labeling of the erythrocytes was performed once 1 day before the onset of the respective study period. Plasma volume was derived from the blood volume by measuring the corresponding hematocrit value (Hct) automatically (Coulter Counter T660) and in parallel by Hct centrifuge.
Blood and Urine Analyses
During study I blood was drawn on the fifth and seventh day (7 AM) of the respective phase to avoid variations in the analyzed parameters due to diurnal changes. During study II blood was drawn on the first and daily on the fourth to seventh day (7 AM). Blood was drawn from subjects in the supine body position without venostasis by catheters inserted 30 min before blood withdrawal. Blood for determinations of arginine vasopressin (AVP), atrial natriuretic peptide (ANP), and renin was collected in ice-chilled tubes. For the analysis of Hct, MCV, and Hb, blood was drawn in EDT tubes at room temperature and was directly analyzed by a Coulter Counter (T660). To analyze serum electrolytes, osmolality, and aldosterone and creatinine concentrations (exclusively study II), blood was collected in tubes without any additive. Samples for hormone determination were immediately separated by centrifugation and stored atUrine was collected throughout both investigations with four sampling
periods per day (7 AM, 1 PM, 7 PM, and 11 PM). Urine volume was
calculated from urine weight and density, respectively. Aliquots were
stored at 80°C until analysis. Serum and urinary creatinine
concentrations were measured according to the Jaffé method
(Boehringer Mannheim). Glomerular filtration rate (GFR) was assessed by
creatinine clearance. Serum and urinary sodium and potassium
concentrations were determined by an ion-selective electrode (Hitachi
604). Serum and urinary osmolality was determined by the method of
freezing point depression (Vogel osmometer type OM 801).
Feces Analysis
During study II consecutive fecal samples were collected for determination of sodium absorption and secretion. Fecal samples were burned to ash (600°C, 90 min). One gram of fecal ash was dissolved in 5 ml 1.5 M sulfuric acid. The sodium concentrations of the solutions were measured by flame photometry.Blood Pressure
During both studies blood pressure was measured by the Riva Rocci method every morning while subjects were in a horizontal body position before getting up. To avoid interobserver variations the measurements in the same volunteers were done by the same personnel each morning.Statistics
Data are presented as means ± SE. All data were statistically compared by ANOVA (repeated-measure design) by using the respective NaCl intake as the "grouping" factor and the sampling day as the "within" factor. A significant effect of NaCl consumption was accepted when a significant influence of NaCl intake on time (day) was evident. Post hoc testing was done by comparing the daily data of each NaCl-consumption level by ANOVA. Furthermore, the changes in body weight, plasma and blood volume, extracellular volume, and in cumulative balances between the first and last study day of the respective NaCl-intake levels were compared by Student's t-test. A linear regression analysis was applied on the data of the last study day to examine dose-effect relationships. In both studies P < 0.05 was considered as the minimum level of significance. ![]() |
RESULTS |
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Fluid Compartments and Body Mass
The stepwise increase in NaCl consumption led to a concomitant significant stepwise increase in plasma volumes (Fig. 1) in both studies (ANOVA study I "NaCl on time effect": P < 0.0001; ANOVA study II: P < 0.05). Starting from a plasma volume of 3,027 ± 76 ml after adaptation to an average NaCl-intake level of 220 meq/day, the plasma volume increased by 7.8 ± 2.6% (P < 0.05) when the NaCl consumption was raised to 440 meq/day. A further increase of 3.5 ± 0.6% occurred when the consumption was raised from 440 to 660 meq NaCl/day in the following 8 days. In total, the elevation of NaCl consumption led to a total rise in plasma volume of 11.4 ± 2.0% (P < 0.0001) from the first until the last period of study I. The subjects of study II started their examinations with comparable plasma volumes in all four groups tested (Fig. 1). The low salt intake of 50 meq/day for 1 wk did not change plasma volumes. However, raising NaCl intake for 1 wk from a normal intake resulted in significant increases in plasma volume of 8.7 ± 2.7% (400 meq/day, P < 0.01) and 13.8 ± 2.9% (550 meq/day, P < 0.01) from the first to the last study day, respectively. A significant plasma volume increase of 300 ± 80 ml (P < 0.05) could also be found by comparing the 550-meq/day treatment and the low-salt-intake group on the last study day. Also, the linear regression analysis confirmed that elevations in NaCl consumption caused a corresponding dose-dependent plasma volume increase (y = 0.00061x + 0.0118; P < 0.001).
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Raising sodium consumption also induced elevations in blood volume
(Fig. 2) in both studies (ANOVA study
I NaCl on time effect: P < 0.001; ANOVA study II
NaCl on time effect: P < 0.01). In study I blood
volumes increased significantly (P < 0.001) by 11.1 ± 1.8%
from the consumption level of 220 to 660 meq NaCl/day, respectively. In
study II the four groups' blood volumes were almost the same at the beginning of the study. After 1 wk, the blood volumes in the
400- and 550-meq-NaCl/day-intake groups were significantly higher
(7.7 ± 2.6, P < 0.05 and 11.9 ± 2.5%,
P < 0.01, respectively) than the values on the respective
first study days of these groups. Also, a significant blood volume
elevation of 724 ± 180 ml (P < 0.05) could be found when
the blood volumes of the 550- and 50-meq NaCl/day groups on the seventh
treatment day were compared. Concomitantly, the linear regression
analysis confirmed that increases in NaCl intake caused significant
dose-dependent blood volume rises (y = 0.148x + 5.175;
P < 0.05).
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On the other hand, total extracellular volumes (Fig.
3), as measured by the inulin-dilution
method, were uninfluenced by the increase in NaCl intake (study
I) despite the significant increases in plasma volumes.
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MCV (Fig. 4) was determined during both
studies to indicate changes in the intracellular compartment. Neither
in study I nor in study II did the rise in nutritive
NaCl consumption lead to an increased MCV (study I: P > 0.05; study II: P > 0.05).
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Figure 5 shows body mass data from both
studies. In study I the subjects began and finished all three
consecutive periods with an unchanged body mass, without any detectable
influence of the NaCl-intake level. In study II body mass did
not increase from the first to the last study day in any of the
NaCl-intake groups. A positive dose dependency between NaCl intake and
body mass was only detectable as a slightly smaller reduction in body mass in the highest NaCl-intake groups (400 meq/day: 0.89 ± 0.24%, P < 0.01 and 550 meq/day:
0.72 ± 0.36%, not
significant) compared with the more pronounced body mass losses in the
low and rather normal NaCl-intake groups (50 meq/day:
1.61 ± 0.17%, P < 0.001 and 200 meq/day:
1.48 ± 0.26%,
P < 0.001).
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Metabolic Balance and Urine Data
Cumulative water balances during both studies are shown in Fig. 6. In study I a significant body fluid loss developed from the first until the eighth day of each treatment period, being most pronounced in the 660-meq-NaCl/day-intake group (P < 0.01). If a water binding effect due to increased NaCl consumption would exist at all, transient tendency of positive water balances on the first day of higher NaCl intake could be attributable to a fluid-retention process. In detail, metabolic fluid balance on the first day of 220-meq NaCl intake (day 1) revealed 188 ± 136 ml, the first day of 440-meq NaCl intake (day 9) 372 ± 62 ml, and the first day of 660-meq NaCl intake (day 17)
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Urine flow during both studies is presented in Tables
1 (study I) and
2 (study II). Before both studies
urine flow of all groups was comparable. The increase in NaCl
consumption, even to extremely high levels of 550 and 660 meq NaCl/day,
never led to a decrease in urine flow that would have been required in
the case of body fluid retention. However, an opposite trend could be
obtained as an acute effect on the first study day in study II:
when the NaCl consumption was reduced to a low-NaCl-intake level of 50 meq NaCl/day, urine flow significantly increased (P < 0.05),
which most likely was the cause for the body fluid loss in this group
at the beginning of the treatment. Thereafter, urine flow reached a
steady state that was not different from the other NaCl-intake groups.
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GFR, which was measured during study II, was almost unchanged during the 1 wk of treatment (Table 2), independent of the NaCl-intake level. Neither the change in NaCl consumption from a rather normal intake level to a low NaCl intake nor the changes to higher NaCl-intake levels for 1 wk, respectively, influenced the GFR.
Figure 7 shows the cumulative sodium
balances during both studies. High NaCl intake in both studies led to
preservation of body sodium that was not paralleled by an increase in
total body water. In study I, doubling of the NaCl consumption
from a rather normal intake of 220 to a high intake of 440 meq/day for
8 days revealed positive sodium balances and as a result led to a
significant (P < 0.01) body sodium storage (Fig. 7A).
Moreover, a further increase in NaCl intake from 440 to 660 meq
NaCl/day for 8 days revealed an additional total sodium storage. On the
respective first day of each phase metabolic sodium balance revealed
51.8 ± 12.0 meq sodium when 220 meq NaCl/day was consumed (day
1), 178.0 ± 28.6 meq sodium on the first day of the 440 meq
NaCl/day phase (day 9), and 168.6 ± 27.3 meq on the first day
of 660 meq NaCl/day (day 17), respectively. At the end of the
entire study period total body sodium content was increased by 1,704.2 ± 309.8 meq sodium (P < 0.001). The results of study
II corresponded to those of study I. The high NaCl intake
of 400 and 550 meq NaCl/day, which are >100% above the average NaCl
ingestion, revealed a significant (ANOVA NaCl on time effect: P < 0.0001) total sodium storage. On the respective first day of each
group, metabolic sodium balance was negative in the group of 50 meq
NaCl/day (151.5 ± 11.8 meq sodium) and in the group of 200 meq
NaCl/day (
32.9 ± 26.1 meq sodium). Those who consumed high
NaCl amounts had positive metabolic sodium balances on the first day.
The group ingesting 400 meq NaCl/day retained 112.6 ± 18.3 meq sodium
on day 1 and the group of 550 meq NaCl/day 78.7 ± 24.4 meq
sodium on day 1. From the first to the last study day the
subjects who consumed 400 meq NaCl/day stored 338 ± 36 meq sodium
(P < 0.001), and those who consumed 550 meq NaCl/day
preserved 202 ± 67 meq sodium (P < 0.05), respectively.
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Table 2 shows the fractional sodium excretion determined during study II. Fractional sodium excretion significantly increased (ANOVA NaCl on time effect: P < 0.0001) with increasing sodium consumption and paralleled the increase in renal sodium excretion. Therefore, changes in tubular sodium reabsorption were most likely the cause for increased sodium excretion.
Tables 1 (study I) and 2 (study II) furthermore show potassium excretion, Na+/K+ ratio and urine osmolality during respective NaCl-intake levels.
Fecal sodium contents were analyzed in study II to include the fecal sodium loss in the metabolic sodium balances. Fecal sodium excretion was uninfluenced by NaCl consumption. The 50-meq-NaCl-intake group excreted 3.0 ± 1.0 meq sodium/day, the 200-meq NaCl group 3.5 ± 1.3 meq sodium/day, and the 400-meq NaCl group 4.2 ± 2.1 meq sodium/day. Even the subjects who consumed 550 meq NaCl/day excreted just 9.9 ± 2.1 meq sodium/day via feces. This shows that sodium excretion via feces is of minor importance for calculating metabolic sodium balances.
Blood Electrolyte and Hormone Levels
Serum electrolyte as well as fluid- and electrolyte-regulating hormone levels are shown in Tables 3 (study I) and 4 (study II). In both studies serum sodium, serum potassium, plasma ANP, as well as serum osmolality, were not influenced by increasing NaCl intake (P > 0.5). When the relative changes of plasma AVP concentrations in both studies are compared no effect due to high NaCl intake was observed (P > 0.05). Moreover, in study II serum osmolality and plasma AVP concentrations showed a tendency to decrease over the study period. Plasma aldosterone levels were significantly suppressed due to higher NaCl consumption (ANOVA NaCl on time effect: study I: P < 0.01, study II: P < 0.0001). Plasma renin levels showed a tendency to decrease in study I (ANOVA NaCl on time effect: study I: P > 0.05) but were significantly suppressed in study II (ANOVA NaCl on time effect: study II: P < 0.0001). However, when the renin and aldosterone concentrations in the group of 400 meq NaCl/day are compared with those in the group 550 meq/day no further suppression could be obtained (ANOVA: P > 0.05), suggesting an already maximal suppression of the system at the NaCl-intake level of 400 meq/day.
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Blood Pressure
Systolic and diastolic blood pressure measured every morning during study I was unaffected by increasing NaCl consumption. On day 8 of the first study phase systolic blood pressure was 121 ± 1 mmHg whereas diastolic pressure revealed 77 ± 1 mmHg, respectively. At the end of the second study phase systolic pressure was 120 ± 1 mmHg and diastolic pressure 73 ± 1 mmHg. It remains the same until the end of the third phase, where systolic pressure was 120 ± 2 mmHg and diastolic pressure 73 ± 1 mmHg (P > 0.05). At the beginning of study II the four groups had comparable blood pressures (50-meq-NaCl-intake group: 113 ± 3 mmHg systolic and 67 ± 4 mmHg diastolic pressure; 200-meq-NaCl-intake group: 109 ± 3 mmHg systolic and 67 ± 3 mmHg diastolic pressure; 400-meq-NaCl-intake group: 107 ± 4 mmHg systolic and 62 ± 3 mmHg diastolic pressure; 550-meq-NaCl-intake group: 109 ± 3 mmHg systolic and 62 ± 3 mmHg diastolic pressure). As during study I increasing NaCl consumption did not induce a rise in blood pressure. After 7 days of different NaCl intake the blood pressure stayed mainly the same (P > 0.05) and revealed on day 7 in the 50-meq-NaCl group: 108 ± 3 mmHg systolic and 64 ± 2 mmHg diastolic pressure, in the 200-meq-NaCl group: 103 ± 2 mmHg systolic and 65 ± 3 mmHg diastolic pressure, in the 400-meq-NaCl group: 107 ± 3 mmHg systolic and 65 ± 3 mmHg diastolic pressure and in the 550-meq group: 108 ± 4 mmHg systolic and 63 ± 3 mmHg diastolic pressure, respectively.The subjects accepted the increase in NaCl intake very well. No symptoms like appearance of edema or headaches occurred.
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DISCUSSION |
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Two independently performed studies indicate a strong dose-effect relationship between plasma volume and NaCl ingestion. In contrast to the rise in intravascular volume, increased NaCl consumption did not affect total extracellular volume under the chosen study conditions. Also, total body water and body mass, which did not increase with increasing sodium intake, do not support the notion that a rise in NaCl ingestion leads to a body fluid storage in healthy male subjects. The present data therefore suggest that chronically applied sodium might not be equally distributed in the extracellular compartment between intravascular and interstitial space. In contrast to the common hypothesis, it appears that high NaCl causes a body fluid shift from the interstitial to the intravascular space to compensate for transiently increasing serum sodium concentrations and serum osmolality. As expected, a chronic high load of alimentary NaCl also caused an increase in renal sodium excretion. However, the rise in urinary sodium excretion was not sufficient to match the level of intake. As a result body sodium was stored without alterations in total body water.
Our data do not confirm the results from several studies where increases in sodium consumption led to body fluid retention (13, 15, 16, 22). The major differences may be that those investigations started with sodium-depleted subjects (15, 16, 22), a condition that does not often occur under normal day-to-day living. In our investigations, however, we intended to adhere as close as possible to normal NaCl consumption, i.e., between 200 and 250 meq sodium/day (3). The different onset levels of sodium intake might therefore have induced different results, meaning body fluid retention and thereby a body mass increase when starting from sodium depletion and unchanged body mass when starting from an average NaCl intake, as in the present studies. On the basis of these results the initial aim of the present studies was to show for the first time a dose-effect relationship among NaCl ingestion, body fluid retention, and distribution of the gained volume over the body fluid compartments, i.e., interstitial space, plasma volume and intracellular volume, when starting from a rather normal NaCl consumption of ~200 meq NaCl/day. To our surprise both study designs, either starting from a balanced state of 220 meq/day NaCl and stepwise increasing NaCl consumption (open-study design) or increasing NaCl consumption per day to 400 or even 550 meq NaCl/day did not lead to a renal fluid retention or any increase in total body fluid. These results are applicable for healthy male subjects. Whether other subjects like women, or those who are older, with various edematous conditions show similar reactions, need further examination. However, the expected effect, a decrease in total body fluid, did occur when NaCl consumption was decreased to 50 meq/day. These observations together with the above mentioned results from the literature may indicate that the starting level of NaCl consumption is very important to induce a sustained body fluid retention. Starting from sodium depletion and increasing NaCl ingestion to levels of 300 or 350 meq/day might induce a renal fluid retention to compensate for the respective transient increases in serum sodium concentrations (23). However, already the average intake level of 220 meq NaCl/day may have activated the sodium-regulating system close to the limits. As a result, a further rise in NaCl consumption to 440 or 660 meq is unable to further expand the system parallel to the intake, and no tremendous change in body fluid retention occurs. These results could fit with the hypothesis of Strauss et al. (25) and Hollenberg (11), who postulated a set point of sodium balance. This set point in a normal, healthy person should be the amount of sodium chloride in the body on a balanced level of zero NaCl intake. Close to this set point a very sensitive regulation should occur, whereas far from the set point the regulating mechanism should be less sensitive. This could explain the fluid retention when starting from a sodium- depleted level, whereas total body fluid remains almost unchanged when starting from an almost normal NaCl ingestion level.
Although total body fluid and extracellular volume did not increase, the increase in NaCl consumption caused, during both studies, a significant increase in plasma volume. The rise in plasma volume might be based on the compensatory reactions of high-salt meals that, each time, induced increases in serum sodium concentration and serum osmolalities 1-2 h after the meal as described by Saville et al. (23). These increases in serum sodium concentrations and serum osmolalities might have caused a volume flux from the interstitial free fluid reservoir into the vessels and thereby a compensation for the increased serum concentrations. With respect to Aukland and Reed (1) compensatory volumes can be transferred from the hydrostatic, colloidosmotic, and lymphatic buffering system of the interstitial space without draining the interstitium. To keep the interstitial electrolyte concentrations almost unchanged, a compensatory volume from the protein-bound fluid reservoir of the interstitial space may then buffer the relative small volume changes of the free fluid reservoir without significant interstitial osmolality changes. As a result the interstitial fluid reservoir could easily be used to decrease serum sodium concentrations without stressing the humoral system.
Because the fluid intake during all study periods was limited to ~3,100 ml/day, dependent on body mass, one might argue that an insufficient, not ad libitum fluid intake has been the cause for the missing rise in total body fluid that should have been induced by increasing NaCl ingestion. In the case of calculating the urinary osmolality in study II according to the equation by Tormey (27), the highest urine osmolality reached values of 1,799 mosmol/kgH2O when 550 meq NaCl/day were consumed. In contrast, already a low sodium intake of 50 meq NaCl/day would reveal a urine osmolality of 773 mosmol/kgH2O when calculating the osmolality on the basis of sodium and potassium excretion. However, when using the freezing-point depression method as a direct method to analyze urine osmolality, urine osmolality reached values of <880 H2O/kg in the highest NaCl-intake group of 550 meq/day in study II and a mean value of 470 mosmol/kgH2O in the group of 50-meq NaCl intake/day. Because the data measured by the direct freezing point depression seems more adequate and the plasma AVP concentrations were not changed due to increasing NaCl intake in both studies, our data do not support the hypothesis of an excessive volume restriction.
The cumulative sodium balances at the end of the 24-day study period and after 7 days of 400 and 550 meq sodium intake/day showed a sodium storage of several grams that was not accompanied by body fluid retention. This effect of a nonquantitative excretion of large amounts of ingested sodium has already been observed by Kirkendall et al. (12). They found a mean sodium excretion of 70-80% of the respective intake in the higher sodium intake groups and discussed the missing part as a loss by sweat or unknown antinatriuretic stimuli. The average invisible weight losses of our test subjects have been 1,489 ± 41 ml (study I) and 1,375 ± 16 ml (study II) at the given temperature of 24°C and humidity of 60%. This is in agreement with Guyton (8), who claimed the daily insensible evaporation by skin and lungs at a rate of 600 ml/day and sodium free. The remaining 800-900 ml fluid loss/day therefore have been lost by sweating. However, sweat sodium concentrations are, dependent on the stimulation of the sweat glands, between 5 meq/l when the sweat glands are only slightly stimulated and 60 meq/l when stimulated strongly (8). However, the measured sodium loss during our preparation study was <5 meq/24 h (fluid loss via skin: 1,450 ± 100 ml), even in the highest NaCl-intake group of 550 meq/day, and thereby underlines the data obtained by Guyton where slightly stimulated sweat glands lead to a sodium loss of ~5 meq/day. As an estimate based on our prestudy data the sodium loss in study I revealed therefore <40 meq in 8 days and in study II ~30 meq in 1 wk. Therefore, even when taking additionally these sweat sodium losses into account the metabolic sodium balance is still highly positive reflecting a sodium storage in the body. One possible explanation for sodium storage without an osmotic effect might be the interstitial space. With respect to Szabó and Magyar (26), who studied the electrolyte concentrations in subcutaneous tissue fluid and lymph in rabbits, in both fluids considerably higher sodium concentrations than in serum can be tolerated. Therefore, an increase in sodium concentrations in interstitial fluid might be a space for the obtained sodium storage.
Summarizing the present results the adaptation of the body to sodium might depend on two basic mechanisms. In the case of sodium-depleted subjects, the adaptation to sodium may be mainly regulated by body fluid retention. In the case of increasing the sodium intake from the normal state the compensatory mechanisms may be different and involve osmotic inactive sodium storage. However, the space that is able to store sodium without a retention of body fluid needs to be investigated in further studies.
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ACKNOWLEDGEMENTS |
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We thank the test subjects for the participation in the study and their excellent compliance. We are grateful to U. Arens and G. Kraus for technical support. A. Boerger and E. Elbert are gratefully acknowledged for preparing the highly palatable diet for the test subjects. We are indebted to P. Kuklinski and his team for help during the test subjects' recruitment and the study. We thank H. M. Wegmann, the recently retired head of the division of medicine, for the opportunity to perform the studies. The Directorate Raumfahrt of DLR is acknowledged for continuous support.
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FOOTNOTES |
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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.
Address for reprint requests and other correspondence: M. Heer, DLR-Institute of Aerospace Medicine, 51170 Cologne, Germany (E-mail: heer{at}pbmail.me.kp.dlr.de).
Received 7 June 1999; accepted in final form 24 November 1999.
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REFERENCES |
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1.
Aukland, K,
and
Reed RK.
Interstitial-lymphatic mechanisms in the control of extracellular volume.
Physiol Rev
73:
1-78,
1993
2.
Denton, D,
Weisinger R,
Mundy N,
Wickings EJ,
Dixson A,
Moisson P,
Pingard AM,
Shade R,
Carey D,
Ardaillou R,
Paillard F,
Chapman J,
Thillet J,
and
Michel JB.
The effect of increased salt intake on blood pressure of chimpanzees.
Nat Med
1:
1009-1016,
1995[ISI][Medline].
3.
Deutsche Gesellschaft für Ernährung.
Ernährungsbericht 1992, edited by Deutsche Gesellschaft für Ernährung e. V.. Frankfurt, Germany: Druckerel Henrich, 1992, p. 85.
4.
Deutsche Gesellschaft für Ernährung.
Empfehlungen für Die Nährstoffzufuhr (5th ed.), edited by Deutsche Gesellschaft für Ernährung. Frankfurt/Main, Germany: Umschau-Verlag, 1991.
5.
Drummer, C,
Gerzer R,
Heer M,
Molz B,
Bie P,
Schloßberger M,
Staedeger C,
Roecker L,
Stroll F,
Heyduck B,
Bauer K,
Warberg J,
Baisch F,
Christensen NJ,
Koenig A,
and
Norsk P.
Effects of an acute saline infusion on fluid and electrolyte metabolism in humans.
Am J Physiol Renal Fluid Electrolyte Physiol
262:
F744-F754,
1992
6.
Drummer, C,
Fiedler F,
Bub A,
Kleefeld D,
Dimitriades E,
Gerzer R,
and
Forssmann WG.
Development and application of a urodilatin (CDD/ANP-95-126)-specific radioimmunoassay.
Pflügers Arch
423:
372-377,
1993[ISI][Medline].
7.
Forbes, GB.
Techniques for estimating body composition.
In: Human Body Composition. New York: Springer-Verlag, 1987, p. 2-17.
8.
Guyton, AC.
Body temperature, temperature regulation, and fever.
In: Textbook of Medical Physiology. Philadelphia, PA: Saunders, 1986, p. 849-853.
9.
Heer, M., C.,
and
Drummer F
Baisch, H. Maass, R. Gerzer, J. Kropp, and Blomqvist G. Effects of head-down tilt and saline loading on body mass, fluid, and electrolyte homeostasis in man.
Acta Physiol Scand
144, Suppl604:
13-22,
1992[ISI].
10.
Heer, M,
Drummer C,
Baisch F,
and
Gerzer R.
Long-term elevations of dietary sodium produce parallel increases in the renal excretion of urodilatin and sodium.
Pflügers Arch
425:
390-394,
1993[ISI][Medline].
11.
Hollenberg, NK.
Set point for sodium homeostasis: surfeit, deficit, and their implications.
Kidney Int
17:
423-429,
1980[ISI][Medline].
12.
Kirkendall, WM,
Connor WE,
Abboud F,
Rastogi SP,
Anderson TA,
and
Fry M.
The effects of dietary sodium chloride on blood pressure, body fluids, electrolytes, renal function, and serum lipids of normotensive man.
J Lab Clin Med
87:
418-434,
1976[ISI].
12a.
Kluthe, B.
PRODI (ed. 4.2). Stuttgart, Germany: Wissenschaftliche Verlagsgesellschaft, 1992.
13.
Kojima, S,
Inoue I,
Hirata Y,
Saito F,
Yoshida K,
Abe H,
Deguchi F,
Kawano Y,
Kimura G,
Yoshimi H,
Yokouchi M,
Kuramochi M,
Ito K,
and
Omae T.
Effects of changes in dietary sodium intake and saline infusion on plasma Atrial natriuretic peptide in hypertensive patients.
Clin Exp Theory Pract
A9:
1243-1258,
1987[ISI].
14.
Krieger, JE,
Liard JF,
and
Cowley AW, Jr.
Hemodynamics, fluid volume, and hormonal responses to chronic high-salt intake in dogs.
Am J Physiol Heart Circ Physiol
259:
H1629-H1636,
1990
15.
Luft, FC,
Rankin LI,
Bloch R,
Willis LR,
Fineberg NS,
and
Weinberger MH.
The effects of rapid saline infusion on sodium excretion, renal function, and blood pressure at different levels of sodium intake.
Am J Kidney Dis
2:
464-470,
1983[ISI][Medline].
16.
McKnight, JA,
Roberts G,
Sheridan B,
and
Atkinson AB.
The effect of low and high sodium diets on plasma atrial natriuretic factor, the renin-aldosterone system and blood pressure in subjects with essential hypertension.
Clin Endocrinol (Oxf)
40:
73-77,
1994[ISI][Medline].
17.
Montz, R.
Das erythrozytaere System.
In: Handbuch Der Medizinischen Radiologie, edited by Diethelm L.,
Heuck F.,
Olsson O.,
Strnad F.,
Vieten H.,
and Zuppinger A.. New York: Springer- Verlag, 1978.
18.
Overlack, A,
Ruppert M,
Kolloch R,
Göbel B,
Kraft K,
Diehl J,
Schmitt W,
and
Stumpe KO.
Divergent hemodynamic and hormonal responses to varying salt intake in normotensive subjects.
Hypertension
22:
331-338,
1993[Abstract].
19.
Pike, RL,
and
Brown ML.
Nutrition: An Integrated Approach. New York: MacMillan, 1984, p. 838.
21.
Robertson, GL.
Regulation of vasopressin secretion.
In: The Kidney: Physiology and Pathophysiology (2nd ed.), edited by Seldin D. W.,
and Giebisch G.. New York: Raven, New York, 1992, p. 1595-1613.
22.
Sagnella, GA,
Markandu ND,
Buckley MG,
Miller MA,
Singer DRJ,
and
MacGregor GA.
Hormonal responses to gradual changes in dietary sodium intake.
Am J Physiol Regulatory Integrative Comp Physiol
256:
R1171-R1175,
1989
23.
Saville, MA,
Geer PG,
Wang BC,
Leadley RJ, Jr,
and
Goetz KL.
A high-salt meal produces natriuresis in humans without elevating plasma atriopeptin.
Proc Soc Exp Biol Med
188:
387-393,
1988[Abstract].
24.
Singer, DRJ,
Markandu ND,
Buckley MG,
Miller MA,
Sagnella GA,
Lachno DR,
Cappuccio FP,
Murday A,
Yacoub MH,
and
MacGregor GA.
Blood pressure and endocrine responses to changes in dietary sodium intake in cardiac transplant recipients.
Circulation
89:
1153-1159,
1994[Abstract].
25.
Strauss, MB,
Lamdin E,
Smith WP,
and
Bleifer DJ.
Surfeit and deficit of sodium.
Arch Intern Med
102:
527-536,
1958[ISI].
26.
Szabo, G,
and
Magyar Z.
Electrolyte concentrations in subcutaneous tissue fluid and lymph.
Lymphology
15:
175-177,
1982.
27.
Tormey, WP.
Are the increasing clinical demands for osmolality measurements and their associated electrolytes appropriate?
Ir J Med Sci
166:
75-79,
1997[ISI][Medline].
28.
Walser, M.
Phenomenological analysis of electrolyte homeostasis.
In: In The Kidney: Physiology and Pathophysiology (2nd ed.), edited by Seldin D. W.,
and Giebisch G.. New York: Raven, 1992, p. 31-44.