Vol. 92, Issue 5, 2097-2104, May 2002
Low sodium intake does not impair renal compensation of
hypoxia-induced respiratory alkalosis
Claudia
Höhne,
Willehad
Boemke,
Nora
Schleyer,
Roland C.
Francis,
Martin O.
Krebs, and
Gabriele
Kaczmarczyk
Experimental Anesthesia, Clinic of Anesthesiology and
Surgical Intensive Care Medicine, Campus Virchow-Klinikum,
Charité, D-13353 Berlin, Germany
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ABSTRACT |
Acute hypoxia causes hyperventilation
and respiratory alkalosis, often combined with increased diuresis and
sodium, potassium, and bicarbonate excretion. With a low sodium intake,
the excretion of the anion bicarbonate may be limited by the lower
excretion rate of the cation sodium through activated sodium-retaining
mechanisms. This study investigates whether the short-term renal
compensation of hypoxia-induced respiratory alkalosis is impaired by a
low sodium intake. Nine conscious, tracheotomized dogs were studied twice either on a low-sodium (LS = 0.5 mmol sodium · kg
body wt
1 · day1) or high-sodium
(HS = 7.5 mmol sodium · kg body
wt1 · day1) diet. The dogs breathed
spontaneously via a ventilator circuit during the experiments: first
hour, normoxia (inspiratory oxygen fraction = 0.21); second to
fourth hour, hypoxia (inspiratory oxygen fraction = 0.1). During
hypoxia (arterial PO2 34.4 ± 2.1 Torr),
plasma pH increased from 7.37 ± 0.01 to 7.48 ± 0.01 (P < 0.05) because of hyperventilation (arterial
PCO2 25.6 ± 2.4 Torr). Urinary pH and
urinary bicarbonate excretion increased irrespective of the sodium
intake. Sodium excretion increased more during HS than during LS,
whereas the increase in potassium excretion was comparable in both
groups. Thus the quick onset of bicarbonate excretion within the first
hour of hypoxia-induced respiratory alkalosis was not impaired by a low
sodium intake. The increased sodium excretion during hypoxia seems to
be combined with a decrease in plasma aldosterone and angiotensin II in
LS as well as in HS dogs. Other factors, e.g., increased mean arterial blood pressure, minute ventilation, and renal blood flow, may have contributed.
hypoxia; acid-base balance; hormones; short-term renal compensation
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INTRODUCTION |
HUMANS AS WELL AS
MANY MAMMALS acutely exposed to hypoxia develop respiratory
alkalosis due to hyperventilation. Consecutively, an increase in
diuresis and sodium-, potassium-, and bicarbonate excretion is
frequently observed (9, 18, 29). The complex renal
response to acute hypoxia seems to be beneficial for the adaptation to
high altitude, where fluid retention may lead to high-altitude sickness
(1). In addition, bicarbonate excretion is a renal
compensatory reaction after acute respiratory alkalosis. Although many
studies exist, the underlying mechanisms responsible for the renal
response to hypoxia and/or hypocapnia are not yet fully understood.
Studies on humans (9) and on animals (8) describe renal excretion of bicarbonate and sodium as a long-term response to hypocapnia. Other studies suggest that only a weak correlation exists between bicarbonate and sodium excretion during hypoxia (18, 29). Furthermore, it remains unclear whether high-altitude natriuresis is compromised under conditions in which sodium-conserving mechanisms are activated (24). It is
well known that, after total body sodium reduction induced by, e.g., peritoneal dialysis combined with a low-sodium diet or repeated mannitol infusion, even strong natriuretic stimuli such as osmotic diuresis or inhibition of aldosterone fail to initiate natriuresis (3).
The objective of the present study was to examine the acute
physiological reactions toward hypoxia-induced respiratory alkalosis on
intact organisms and to determine whether the renal compensatory response would be impaired by a low sodium intake.
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MATERIALS AND METHODS |
Animals, maintenance, and diets.
A total of 18 experiments were performed on nine purebred female beagle
dogs (body wt 12.6 ± 0.9 kg) with two experiments on each dog.
The dogs were obtained from the Central Animal Facilities of the
Humboldt-University in Berlin. They were tested for their social
behavior and tolerance to urinary bladder catheterization and
intravascular cannulas. The permission to perform the experiments was
obtained from the Governmental Animal Protection Committee (AZ
G0183/97).
The dogs were kept under highly standardized conditions:
air-conditioned animal room during the day and large individual kennels (5 m2) during the night (21°C, 55% humidity). General
status, body temperature, and body weight were checked daily. A
permanent tracheotomy was performed 4-5 wk before the experiments
(for details, see Refs. 14 and 18). Thereafter, the dogs
were trained to lie quietly on their right side on a padded animal
table for at least 5 h.
Beginning at least 7 days before the experiments, the dogs were fed
either of two standardized diets. The diet consisted of minced beef (12 g) and boiled rice (58 g) and contained 91 ml water and 3.5 mmol
potassium (all values were given per kg body wt per day). In one
protocol, the sodium intake was low (0.5 mmol Na · kg body
wt1 · day1), and, in addition, 20 mg furosemide (Furosemid, ratiopharm, Ulm, Germany) were given
intravenously at the 7th and 6th day before the experiments. The
low-sodium diet and furosemide application were chosen to activate
sodium-retaining mechanisms. In the other protocol, the sodium intake
was high (7.5 mmol Na · kg body
wt1 · day1). The calories supplied
with these diets (277 kJ · kg body
wt1 · day1) were sufficient to keep
the dog's body weight constant for weeks. The food mash was given once
a day at 2 PM, and the intake was finished by all dogs within 1 h.
No further intake was allowed until feeding on the next day.
Eight days before an experiment, 100 ml of the dog's own blood were
collected via puncture of a foreleg vein and stored in a blood bag at
4°C (Biopack, Biotrans, Dreieich, Germany). The blood served to
replace the blood withdrawn for analysis during the experiments. No
other fluids were administered during the experiments.
After completion of the studies, the tracheotomy was surgically closed,
and the dogs were handed to private persons with the assistance of our
university veterinarians.
Procedures during the experiments.
Preparation of the dogs started at 7:30 AM. Body weight and temperature
were recorded. The urinary bladder was catheterized with a
self-retaining Foley catheter. A foreleg vein was punctured, and an
infusion of creatinine was started (priming dose 1.4 g for 30 min,
maintenance infusion 4.7 mg/min) for assessment of glomerular
filtration rate (exogenous creatinine clearance). After local
anesthesia (lidocaine 1%, Braun Melsungen, Germany), an arterial line
(20 G, no. 4235-8, Ohmeda, Erlangen, Germany) was advanced into the
abdominal aorta via the femoral artery and a pulmonary artery catheter
(5 Fr, no. 132F5, Baxter, Unterschleissheim, Germany) was inserted via
the right external jugular vein. The catheters were used for continuous
systemic and pulmonary blood pressure monitoring, cardiac output
measurements, and blood sampling. After catheter insertion, the dogs
were placed on the padded animal table and positioned on their right
side. The pressure transducers were adjusted to the level of the right
atrium. The distance between transducer and table was recorded and also
used for the next experiment on this individual dog. Finally, the
tracheal tube was inserted, blocked, and connected to the ventilator
set to continuous positive airway pressure mode with 4 cmH2O of continuous airway pressure. Thereafter, the
conscious dogs were given 60 min to adjust to the experimental situation.
Each of the nine dogs was studied twice in randomized order:
1) on the low-sodium diet (LS) and 2) on the
high-sodium diet (HS). The interval between the two experiments on the
same dog was at least 14 days.
In both experiments (LS and HS) the dogs breathed room air (21%
O2, 79% N2; normoxia) for 1 h, followed
by breathing a gas mixture containing 10% O2 and 90%
N2 for 3 h (hypoxia).
Mean arterial blood pressure (MAP), heart rate (HR), central venous
pressure, pulmonary arterial pressure, and minute ventilation (using
the flow transducer in the ventilator) were measured continuously and
the data stored on a computer. Cardiac output was measured by using the
thermodilution technique (5-ml injection volume at 5-10°C;
Vigilance, Baxter Edwards Critical Care). Five consecutive measurements
were performed. The highest and lowest values were rejected. The mean
cardiac output was calculated from the remaining three determinations
and taken for calculation of systemic and pulmonary vascular resistance
by standard formulas.
At the end of each experimental hour, blood samples were taken to
determine arterial blood gases, actual bicarbonate, base excess, plasma
electrolytes, lactate, hormones, and creatinine. The blood withdrawn
was immediately replaced with an equal amount of the dog's own stored
blood using a blood filter system (TNSB-3, Biotest, Alzenau, Germany).
At hourly intervals, renal sodium, water, potassium, bicarbonate,
chloride, phosphate, calcium, and creatinine excretions were measured
after complete evacuation of the urinary bladder (air washout).
Exogenous creatinine clearance was calculated by the standard formula
to assess glomerular filtration rate.
Measurement of urinary and plasma values.
Urinary sodium and potassium concentrations were measured by flame
photometry (Photometer Eppendorf, Hamburg, Germany). Urinary calcium
concentration was determined by photometric reaction, urinary chloride
concentration by ion-specific electrodes, urinary phosphate
concentration by malachite green reaction, and creatinine with a
creatinine analyzer (modified Jaffé reaction; Beckmann Instruments).
Blood gas analysis, plasma sodium, potassium, calcium, and chloride
measurements were performed at hourly intervals (ABL 505, Radiometer,
Copenhagen, Denmark). Plasma and urinary bicarbonate concentrations
were calculated using the Henderson-Hasselbalch equation. The plasma
potassium concentration used for blood was 6.1; the plasma potassium
concentration used for urine was 6.33 
0.5 · B1/2 (where B represents the total
cation concentration estimated as the sum of sodium and potassium
expressed in equivalents per liter). The solubility coefficients
applied for CO2 were 0.0301 for blood and 0.0309 for urine.
Arterial lactate was determined by the reduction of NAD with lactate
dehydrogenase (Abbott ABA100 system).
Procedures for analysis of plasma renin activity (PRA), angiotensin II
concentration, plasma aldosterone concentration, and atrial natriuretic
peptide have been described previously (14).
Statistical analysis.
All values are given as means ± SE (n = 9).
Intergroup comparison, i.e., LS vs. HS during the respective normoxia
and hypoxia period, was performed using Student's t-test.
For intragroup comparisons (time course) a general linear model of
analysis of variance for repeated measures was applied (SPSS 9.0, Chicago, IL). Post hoc testing of the means was performed with
Student's t-test with Bonferroni correction for multiple
comparisons. Regression analysis was used to determine the correlations
between minute ventilation and urine volume and between renal
bicarbonate excretion and renal sodium and potassium excretion,
respectively. Statistical significance was considered at
P < 0.05.
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RESULTS |
Minute ventilation, arterial blood gases, and plasma pH.
With hypoxia, arterial O2 tension
(PaO2) decreased from ~98 Torr to 35-38
Torr in both groups (P < 0.05; Table
1). Minute ventilation increased by
1.3-1.6 l/min on both diets (Table 1). Because of the increase in
minute ventilation (P < 0.05), the arterial carbon
dioxide tension decreased similarly in both groups from 34 ± 1 Torr during normoxia to 27 ± 1 Torr during hypoxia (P < 0.05; Table 1). Plasma pH increased during
hypoxia (P < 0.05; Table 1). Base excess was slightly
negative in both groups and increased during hypoxia (P < 0.05; Table 1).
Plasma values and plasma hormones.
Plasma actual bicarbonate concentration (18.1-19.5 mmol/l; Table
1), plasma sodium concentration (143-147 mmol/l), and plasma osmolality (295-300 mosmol/l) were similar in both groups and remained unchanged during hypoxia. Plasma potassium concentration decreased during hypoxia in LS as well as in HS experiments
(P < 0.05; Table 2).
Plasma calcium concentration decreased slightly in the LS dogs
(1.35 ± 0.01 to 1.33 ± 0.01 mmol/l) as well as in the HS
dogs (1.38 ± 0.01 to 1.33 ± 0.02 mmol/l; P < 0.05); plasma chloride concentration decreased from 110 ± 0.8 (LS and HS) to 108 ± 0.7 mmol/l (LS and HS) during hypoxia
(P < 0.05). Plasma lactate concentration (2.7-3.1
mmol/l) was similar in both groups and remained unchanged during
hypoxia. PRA (Table 2), angiotensin II (Table 2), and plasma
aldosterone concentrations (Fig. 1) were
always lower in the HS dogs (P < 0.05) and
decreased during hypoxia in both protocols. The decrease was more
pronounced in LS than in HS dogs (P < 0.05). Plasma
concentrations of atrial natriuretic peptide (42-53 pg/ml) were
similar in both protocols and did not change during hypoxia in either
protocol (Table 2).
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Fig. 1.
Plasma aldosterone concentration during 1 h of
normoxia (21% inspiratory O2 concentration) and 3 h
of hypoxia (10% inspiratory O2 concentration). LS,
low-sodium diet; HS, high-sodium diet. Values are means ± SE
(n = 9). *P < 0.05 vs. normoxia;
§P < 0.05 vs. LS.
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Renal function data.
Urine volume and urinary potassium excretion increased similarly during
hypoxia in LS as well as in HS dogs (P < 0.05; Table 3). Minute ventilation correlated with
urine excretion in LS (r = 0.72, P = 0.03) but not in HS dogs (r = 0.66, P = 0.052; Fig. 2). Urinary sodium excretion
(Fig. 3) and fractional excretion of
sodium (Table 3) during hypoxia were much greater in HS dogs than in LS
dogs (P < 0.05). For comparison, the individual values of plasma aldosterone, sodium excretion, and urine volume on both diets
are given in Table 5. No correlation of delta (delta = normoxia hypoxia values) PAC/UNaV or delta
PAC/UV was found (P > 0.05) (where PAC is
plasma aldosterone concentration, UNaV is urinary sodium
excretion, and UV is urine volume). Urinary chloride excretion was also
greater in HS (1.6 ± 0.3 µmol · kg body
wt1 · min1) than in LS dogs
(0.8 ± 0.2 µmol · kg body
wt1 · min1; P < 0.05) but did not change during hypoxia. Urinary bicarbonate excretion
increased during hypoxia in both groups (P < 0.05;
Fig. 3). Bicarbonate excretion correlated with urinary potassium
excretion in both groups (LS: r = 0.75, P = 0.01; HS: r = 0.85, P = 0.04; Fig. 4),
whereas it correlated with urinary sodium excretion in HS dogs only
(HS: r = 0.85, P = 0.01; LS:
r = 0.28, P = 0.5; Fig. 5). Urinary calcium (12-30
nmol · kg body wt1 · min1),
phosphate (0.05-0.3 µmol · kg body
wt1 · min1), and osmolal excretion
(12-16 µosm · kg body
wt1 · min1) were similar in both
groups and did not change during hypoxia. Urinary pH increased in both
groups during hypoxia (P < 0.05; Table 3). Glomerular
filtration rate (3.5-3.9 ml · kg body
wt1 · min1) did not change during
hypoxia in either protocol.
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Fig. 2.
Minute ventilation of each LS (A;
n = 9) and HS (B; n = 9) dog
during hypoxia (3rd hour) plotted against urine excretion in the same
time period.
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Fig. 3.
Urinary sodium and bicarbonate excretion during 1 h
of normoxia (21% inspiratory O2 concentration) and 3 h of hypoxia (10% inspiratory O2 concentration). Values
are means ± SE (n = 9). *P < 0.05 vs. normoxia; §P < 0.05 vs. LS.
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Fig. 4.
Mean urinary potassium excretion of each LS
(A; n = 9) and HS (B;
n = 9) dog during hypoxia (3rd hour) plotted against
urinary bicarbonate excretion in the same time period.
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Fig. 5.
Mean urinary sodium excretion of each HS dog
(n = 9) during hypoxia (3rd hour) plotted against
urinary bicarbonate excretion in the same time period.
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Hemodynamics.
During hypoxia, HR, cardiac output, MAP, mean pulmonary arterial
pressure, and pulmonary vascular resistance increased to a similar
extent in HS as well as in LS dogs (P < 0.05; Table 4), whereas central venous pressure
(1.2-1.8 cmH2O) and systemic vascular resistance
(3,739-3,903 dyn · s · cm5)
remained stable in both protocols.
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DISCUSSION |
The aim of the present study was to determine whether short-term
renal compensation after acute hypoxia-induced respiratory alkalosis is
impaired by a low-sodium intake. Experiments were performed on nine
trained, conscious beagle dogs, each of whom was studied on both a low
and high-sodium diet. In the 4-h protocol, the dogs breathed room air
for 1 h and thereafter a hypoxic gas mixture for 3 h. The
results demonstrated that during 3 h of hypoxia neither the time
course nor the extent of acute respiratory alkalosis were affected by
the dietary salt intake. Acute renal bicarbonate excretion was observed
on both diets but could not compensate for the respiratory alkalosis
within the observation period.
Urinary bicarbonate excretion.
Acute hypoxia induces an increase in alveolar ventilation and results,
through hyperventilation, in respiratory alkalosis. One of our aims was
to determine whether a low sodium intake would deteriorate respiratory
alkalosis by impairing renal compensatory mechanisms. An organism with
all its regulatory mechanisms intact will strive to bring back plasma
pH from alkalotic to normal in this situation. There are several ways
by which this can be accomplished, e.g., by decreasing
NH
and titratable acid excretion and by reducing the
rate of H+ secretion. Most importantly, however, the kidney
responds to hypocapnia with an increase in bicarbonate excretion
(5, 6). In our dogs, the onset of bicarbonate
excretion starts within the first hour of hypoxia and increases
throughout the 3-h observation period (Fig. 3). This did not prevent
plasma pH from increasing during hypoxia, however, and there was no
difference in the magnitude of respiratory alkalosis between the LS and
HS dogs (Table 1). This is not what we had expected. We assumed that
after 7 days on a low sodium intake and two times furosemide (on
days 6 and 7 before the study) the "need" to
save sodium would restrict its excretion as an accompanying cation for
the anion bicarbonate. We presumed that on the LS diet the dogs would
be in a conflicting situation during hypoxia: bringing back plasma pH
to normal by, e.g., sodium bicarbonate excretion on the one hand and
preventing sodium loss on the other. In our short-term experiments on a
low sodium intake, the dogs increased sodium excretion more than
twofold and seemed to excrete sodium partly as sodium bicarbonate
despite the presumed need to conserve sodium, because of the low sodium intake. The prime bicarbonate compound in LS dogs seems to be potassium
bicarbonate, however. This was also shown to happen in healthy humans
exposed to chronic hypocapnia (9). In the present study,
potassium excretion increased about threefold during hypoxia in both
groups (Table 3), which is in agreement with the observations of
Gledhill et al. (9) in humans. We found a strong
correlation between bicarbonate and potassium excretion in both groups
(Fig. 4), whereas bicarbonate correlated with sodium excretion in the
HS dogs only (Fig. 5). This indicates that, during a low sodium intake,
bicarbonate excretion is more related to potassium than to sodium excretion.
Urinary sodium excretion.
Despite a great number of studies, the literature about natriuresis
during hypoxia is quite conflicting. In humans, Swenson et al.
(29) found natriuresis after 6 h of hypoxia, whereas others, after 2 h of hypoxia, found no natriuresis in humans
(13) or rats (12). It is known that a
standardized sodium and water intake, as in our and in Swenson et
al.'s study (29), has a great impact on the rate of renal
electrolyte excretion, with and without hypoxia. This could be one of
the reasons for the conflicting results between these and the other
studies. Otherwise, it has to be assumed that the renal response toward
hypoxia or respiratory alkalosis is faster in dogs than in other mammals.
Several factors have been proposed to initiate natriuresis during
hypoxia, e.g., respiratory alkalosis (15, 19, 22, 30) or
hypoxia per se. Whatever the cause may be, sodium excretion during
acute hypoxia seems to be a tubular process because we found an
increased fractional sodium excretion but no change in glomerular
filtration rate. The markedly decreased PRA, angiotensin II, and plasma
aldosterone concentrations during hypoxia may partly account for this
finding and the natriuresis observed (Tables 2 and
5). However, when delta values of urine
sodium or volume excretion were correlated with delta aldosterone
values, no good correlation was found, indicating that there must be
additional factors involved that increase sodium and volume excretion
during hypoxia. Irrespective of this poor correlation, the decrease of sodium-retaining hormones during hypoxia is in accordance with both
previous studies from our laboratory (14, 18) and studies from other authors (23, 31). The decrease was more
pronounced in the LS than in the HS dogs because of the preexperimental
stimulation of the renin-angiotensin-aldosterone system through the low
sodium intake (Fig. 1, Tables 2 and 5).
The reasons for the decrease in PRA during hypoxia are manifold.
1) The increase in arterial blood pressure and thus renal perfusion pressure during hypoxia (MAP was ~98 mmHg during normoxia and ~109 mmHg during hypoxia) may have reduced PRA via the renal baroreceptor mechanism (Table 4). However, a MAP increase of ~10 mmHg
in this pressure range is usually not followed by such a striking
decrease in PRA, at least not in normoxic dogs (7, 27).
2) A recent study from our laboratory suggests that the decrease in PRA during hypoxia may be mediated by adenosine
(14). 3) In addition, endothelins were shown to
suppress renin secretion in vitro (20) and in vivo
(26), possibly via endothelin A receptor-dependent
mechanisms. 4) Finally, nitric oxide (NO) may be involved,
because NO synthase inhibition was shown to reduce PRA levels in
conscious normoxic dogs (28).
The decrease in plasma aldosterone during hypoxia, which was observed
with both diets, is generally assumed to be due to the reduced
conversion from cortisol to aldosterone by 18-hydroxylase during
hypoxia (4) and occurs independent from the decrease in
PRA and angiotensin II (14). In addition, the slight
decrease in plasma potassium concentration (0.2 mmol/l) may have
contributed to the decrease of aldosterone (Table 2). This decrease in
plasma potassium concentration is most probably a result of
hypoxia-induced respiratory alkalosis shifting potassium from the
extracellular to the intracellular space (5).
In addition to hormonal and/or neuronal factors
(14-16), the increase in MAP during hypoxia possibly
contributed to sodium and water excretion via the pressure
natriuresis-diuresis mechanism (10, 11, 21, 25).
Furthermore, an increase in renal blood flow during hypoxia may have
contributed to sodium and water excretion (21).
Although sodium excretion increased on the high-sodium as well as on
the low-sodium diet, the percent increase in sodium excretion during
hypoxia was blunted during the low sodium intake (Fig. 3). This could
be due to the presence of sodium conserving mechanisms, e.g., by the
overall higher aldosterone, angiotensin II, and PRA levels on the LS
diet. How far different activities of the NO system on a low and a high
sodium intake are involved remains to be determined (2).
Urine volume during hypoxia.
Compared with sodium excretion, the increase in urine volume was more
pronounced during the first hour of hypoxia and continued to increase
at a lower pace during the following 2 h (Table 3). Our findings
are in line with studies in rats (12) and humans (13) demonstrating that the onset of increased urine
volume can be observed within the first 2 h of hypoxia. However,
it is still unknown which specific mechanisms are responsible for
hypoxic diuresis.
Honig (15) postulates a direct link between peripheral
chemoreceptor stimulation and renal water and sodium excretion from studies on hypoxic, isolated perfused carotid bodies. Swenson et al.
(29) speculate that a high hypoxic ventilatory
responsiveness might predict the magnitude of hypoxia-induced diuresis
and natriuresis. In the present study, minute ventilation increased
quickly in both groups (Table 1), but only in the LS dogs was the
correlation between minute ventilation and urinary volume excretion
found to be significant (Fig. 2).
Hemodynamics.
Despite signs of general sympathetic stimulation (increase in HR, MAP,
cardiac output, and minute ventilation; Tables 1 and 4), the increase
in renal sympathetic nerve activity was not powerful enough to induce
an increase in PRA levels and sodium and/or water retention during
hypoxia (Fig. 3, Table 4).
Pulmonary arterial pressure and pulmonary vascular resistance increased
on both diets as a sign of hypoxic pulmonary vasoconstriction (Table
4).
In summary, we have shown that the increase in diuresis and natriuresis
during hypoxia corresponded mainly with a decrease in angiotensin II
and plasma aldosterone concentration in our conscious resting dogs.
Other factors such as increased MAP (10, 11, 25),
increased minute ventilation (29), and possibly increased
renal blood flow (21) probably contributed to the renal response. Renal bicarbonate excretion after hypoxia-induced respiratory alkalosis was not influenced by the amount of sodium intake
during 3 h of hypoxia. It cannot be excluded, however, that 3 h of hypoxia were too short a period to show advantages or
disadvantages of either diet. Looking at Fig. 3, one gets the impression that bicarbonate excretion in the HS dogs starts to gain
over the LS dogs after 3 h. Because of the practical relevance, e.g., for mountaineers, well-controlled long-term experiments with
respect to compensation of respiratory alkalosis on different sodium
intakes are recommended.
| |
ACKNOWLEDGEMENTS |
The authors are indebted to Rainer Mohnhaupt for help with the
statistics, to Birgit Brandt and Daniela Bayerl for expert technical
assistance, and to April M. Kurzke for editorial help.
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FOOTNOTES |
This study was supported by a grant from the Deutsche
Forschungsgemeinschaft to Gabriele Kaczmarczyk (Ka 526/5-2).
Part of this work was presented at the 13th ESICM Annual Congress in
Rome, Italy, 2000.
Address for reprint requests and other correspondence: C. Höhne, AG Experimentelle Anaesthesie, Campus Virchow-Klinikum, Medizinische Fakultät der Charité, Augustenburger
Platz 1, D-13353 Berlin, Germany (E-mail:
claudia.hoehne{at}charite.de).
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. Section 1734 solely to indicate this fact.
First published December 14, 2001;10.1152/japplphysiol.00719.2001
Received 10 July 2001; accepted in final form 5 December 2001.
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ABSTRACT
INTRODUCTION
E in LS and HS groups