Clinical Science (1982) 6 2 . 4 3 4 9
43
Body-fluid composition in normal and hypertensive man
J. H. BAUER A N D C. S . BROOKS
Research and Medical Services, The Harry S. Truman Memorial Veterans Hospital, and the Department of Medicine,
The University of Missouri Medical Center, Columbia, MO, USA.
(Received 5 January129 June 1981; accepted 23 July 1981)
Summary
Introduction
1. Erythrocyte mass, plasma volume (PV),
extracellular fluid volume (ECFV) and total body
water were simultaneously measured in 30
normotensive and 30 normal-renin hypertensive
Caucasian male subjects for accurate determination of the presence or absence of a
disorder(s) in body-fluid composition in hypertension.
2. The results indicate that plasma volume and
total blood volume are lower in hypertensive
subjects than in normotensive control subjects.
The PV comprised 19% of the ECFV in both
control and hypertensive subjects.
3. ECFV was lower in hypertensive subjects
than in normotensive control subjects; the PV
and interstitial fluid components of the ECFV
were reduced by similar proportions. The ECFV,
furthermore, comprised a smaller portion of the
total body water in hypertensive subjects than
that in control subjects.
4. We conclude that in the hypertensive state
there is a reduction in the ECFV, but that there is
no change in the partition of the ECFV between
the plasma and interstitial components.
The relation between salt and water balance and
blood pressure is well recognized. However, the
differences in body-fluid composition between
normotensive and hypertensive subjects remain
controversial. The purpose of the present study
was to compare the body-fluid composition of
normotensive and normal-renin hypertensive
Caucasian male subjects by measuring their
erythrocyte mass, plasma volume (PV), extracellular fluid volume (ECFV) and total body
water. We have reported 1I similar studies comparing age-matched normotensive and mildly
hypertensive subjects under 35 years of age. In
our present study the number of control observations was extended to include subjects over the
age of 35 years, and the study was restricted to
subjects of a narrow weight range to improve the
matching of the two groups. This study extends
previous observations by others on the body-fluid
composition in subjects with mild-to-moderate
normal-renin essential hypertension [21.
Key words: extracellular fluid volume, interstitial
fluid volume, intracellular fluid volume, normalrenin hypertension, plasma renin activity, plasma
volume, total body water.
Subjects
Abbreviations: ECFV, extracellular fluid volume;
ICFV, intracellular fluid volume; PV, plasma
volume.
Correspondence: Dr John H. Bauer, Medical
Service (111), The Harry S. Truman Memorial
Veterans Hospital, Columbia, MO 65201, U.S.A.
0143-5221/82/010043-07S01.50/1
Methods
These studies were done at the University of
Missouri Medical Center, Clinical Research
Center in Columbia, MO, U.S.A. Informed
consent was obtained and research was carried
out according to the principles of the Declaration of Helsinki. All studies were approved
by the Harry S. Truman Memorial Veterans
Hospital and the University of Missouri Joint
Committee for Research Involving Human Subjects.
The control subjects were 30 normal
Q 1982 The Biochemical Society and the Medical Research Society
J . H . Bauer and C . S . Brooks
44
Caucasian healthy male volunteers who had no
history of hypertension and had casual outpatient systolic blood pressures of less than 140
mmHg and diastolic blood pressures of less than
90 mmHg. Their ages ranged from 22 to 65
years and their weights ranged from 70 to 92 kg.
The hypertensive subjects were 30 Caucasian
male volunteers who had mild-to-moderate
hypertension with diastolic blood pressure ranging from 90 to 115 mmHg and who maintained a
casual 5 min recumbent outpatient systolic blood
pressure greater than 140 mmHg (first phase of
the Korotkoff sounds) and a diastolic blood
pressure greater than 90 mmHg (fifth phase), as
measured with a mercury sphygmomanometer on
three repetitive visits at weekly intervals. They
were on an unrestricted diet and had been without
drug therapy for 3 weeks. Their ages ranged from
21 to 6 5 years and their weights ranged from 70
to 92 kg. All exhibited absence, or only minor
degrees, of cardiac, renal or vascular impairment. Specifically excluded were persons with
diabetes mellitus, peripheral vascular disease,
cardiomegaly, congestive heart failure, renal
insufficiency (creatinine clearance less than 60
ml/min per 1-72 m2), proteinuria or grade 3 or 4
Keith-Wagener hypertensive retinopathy.
Protocol
In order to compare the body-fluid composition of normotensive and normal-renin hyper-
tensive subjects, Caucasian males with a body
weight between 70 and 92 kg underwent a
prospective evaluation of body-fluid composition
(volume studies) and dynamic renin-aldosterone
profile (humoral studies) as outlined in Table 1.
Only hypertensive subjects demonstrating a
normal renin-aldosterone profile, as compared
with age-matched normotensive control subjects,
are reported in this study.
Volume studies
Simultaneous volume studies were done on day
2 of the protocol as described by Bauer et al. [31.
Radioactive isotopes and average dosages used
were: 51Cr-labelled erythrocytes, 10 pCi (for
erythrocyte mass); l2’I-labe1led human serum
albumin, 5 pCi (for PV); sodium [35Slsulphate,75
pCi (for ECFV) and tritiated water, 90 pCi (for
total body water). Total blood volume was
calculated by adding erythrocyte mass and
plasma volume. Interstitial fluid volume was
calculated by subtracting PV from ECFV. Intracellular fluid volume (ICFV) was calculated by
subtracting ECFV from total body water. Wholebody packed cell volume (PCV) was calculated
by dividing erythrocyte mass by total blood
volume and the ratio of whole-bodyharge-vessel
(peripheral vein) PCV (F,,,, ratio) was also
calculated. Bauer et al. [31 have reported duplicate studies in human subjects demonstrating less
than 4% variation for all body-fluid spaces
TABLE1. Protocol f o r control and hypertensive subjects
Dayno.
Time
(hours)
Procedure
I
12.00
2
24.00
08.00
Admission to Clinical Research Center: history and physical examination; weight and height measurements;
unrestricted fluids and diet
Start of overnight fast
Basal blood pressure and heart rate determinations (10 measurements with a mercury sphygmomanometer);
overnight recumbent humoral and blood chemistry studies; begin 24 h urine for electrolytes and creatinine
Volume studies (see the text)
Unrestricted fluids and diet
Start of overnight fast
Assumption of 2 h upright posture
Upright (before saline infusion) humoral studies; terminate 24 h urine; start of absolute bedrest; start of infusion
of saline ( 5 0 0 ml/h)
Termination of saline infusion; recumbent (aRer saline infusion) humoral studies; unrestricted fluids and diet
Start of overnight fast
Assumption of 2 h upright posture
Upright (before frusemide administration) humoral studies; start of constant diet: 10 mmol of sodium and
70 mmol of potassium; fluid restriction: weight (kg) x 24 ml of distilled water
3
4
08.30
12.00
24.00
06.00
08.00
12.00
24.00
06.00
08.00
Administration of frusemide (40 mg orally)
5
18.00
24.00
06.00
08.00
12.00
Start of overnight fast
Assumption of 2 h upright posture
Upright (after frusemide administration) humoral studies; high-salt diet and unrestricted fluids
Discharge
Body-jluid composition
measured. Cumulative radiation exposure was
estimated to be less than 100 mrads.
45
Insufficient numbers of patients with high-renin
essential hypertension have yet been studied.
Chemical analysis
Humoral studies
Plasma renin activity assay. Venous blood was
collected in chilled test tubes containing ethylenediaminetetra-acetic acid (EDTA) and spun in
a refrigerated centrifuge to separate plasma. The
pH of 1 ml of plasma was adjusted to approximately 5 - 5 by adding citric acid (0.38 mol/l).
Approximately 7 pg of di-isopropyl fluorophosphate was added to each sample to inhibit
converting enzymes. All samples were incubated
at 37OC for 30 min. Then, 10 pl of each sample
was assayed as described previously for radioimmunoassay of generated angiotensin I [41.
Plasma aldosterone assay. Venous blood was
collected in chilled heparin-containing test tubes
and spun in a refrigerated centrifuge to separate
plasma. Plasma samples (1 ml) were extracted
with 11 ml of methylene chloride plus three drops
of sodium hydroxide and hydrochloric acid (0.1
mol/l) and subsequently rinsed with distilled
water. Samples were dried under N,, and the
extract was placed on a glass column (60 cm x 1
cm) prepared with Sephadex LH-20M in dichloromethane/methanol (98:2, v/v). A 60-72 ml
fraction containing the aldosterone was eluted,
dried under N, and reconstituted with 200 pl of
ethanol. A 50 pl portion of the reconstituted
sample was assayed as described previously for
radioimmunoassay of aldosterone [51.
Renin-aldosterone profile. A 3 day protocol
(days 3 , 4 and 5 in Table l), adapted from that of
Grim et al. [a], was used to evaluate e dynamic
responses of the renin-aldosterone s tem (Table
3). In our laboratory low-renin hypertension is
defined as the failure of plasma renin activity to
stimulate to greater than 4 . 0 ng h-' ml-' after the
low sodium diet, 120 mg of frusemide and an
upright posture. In our laboratory the mean f SD
for normal subjects is 26.7
13-8 ng h-I ml-I
(range 4.7-56.7 ng h-' ml-l). High-renin hypertension is defined as the failure of plasma renin
activity to suppress to less than 2.0 ng h-I ml-I
after infusion of sodium chloride solution (150
mmol :saline) and a recumbent posture. In our
laboratory the mean f SD for normal subjects is
0 - 9 f 0 . 3 ng h-' ml-' (range 0.5-1.9 ng h-'
ml-').
Excluded from the present study were hypertensive patients with either low- or high-renin
profiles. Our observations on body-fluid composition in subjects with low-renin essential
hypertension have been reported previously [ 11.
$
Sodium, potassium, chloride, glucose, urea
nitrogen and creatinine concentrations in serum
or urine were measured with the Auto-analyzer I1
(Technicon Instruments, Tarrytown, NY,
USA.). Serum total carbon dioxide was determined by a pH blood gas analyser and acid-base
calculator (Instrument Laboratories 5 13). Urine
electrolyte data were expressed as mmol/g of
creatinine.
Statistics and expression of bodyfluid volumes
Data were statistically analysed by Student's
t-test, and differences were regarded as significant if P was less than 0-05. Linear (least
squares) regressions and correlation coefficients
were calculated for the relations between bodyfluid volumes and age, and diastolic and systolic
blood pressures.
The difficulty in selecting an appropriate index
of reference to express body-fluid volumes has
been reviewed by Tarazi [ 21. We have previously
correlated each body fluid space with surface
area, body weight and body height and found
significant correlations between PV (expressed as
litres) and body weight (expressed as kg): r =
0.7346, P < 0.001; and between PV (expressed
as litres) and body height (expressed as cm): r =
0.5622, P < 0.001 [ 11. Positive correlations were
also found between ECFV and total body water
(expressed in litres) to body weight and height
[l]. When volume indices were expressed as a
function of surface area (l/m2), the significance of
the correlations was lost. Therefore we have
chosen to express, statistically analyse and
interpret volume data as a function of surface
area, calculated from the nomogram of DuBois &
DuBois [71. For comparative purposes, we have
expressed and statistically analysed volume data
as an absolute value (litres) and as a function of
weight (ml/kg).
Results
Patient characteristics
Control and hypertensive subjects were
matched for weight and surface area (Table 2).
Although control subjects were younger than
hypertensive subjects, all body-fluid volume
determinations were independent of age when
J. H . Bauer and C . S . Brooks
46
TABLE
2. Subject characteristics
Results are means k SEM. Significances of comparisons between normotensive (control) and
hypertensive subjects are shown. N.S.,Not significant.
Age (years)
Weight (kg)
Surface area (m’)
Basal blood pressure (systolic, mmHg)
Basal blood pressure (diastolic, mmHg)
Basal heart rate (beatdmin)
Control
subjects (n = 30)
Hypertensive
subjects (n = 30)
P
37.6 f 2.6
79.9 f 1 . 1
1.99 f 0.01
113f2
71 f 1
62k 1
45. I f 2.2
82.2 f 1 . 1
I .95 f 0.02
142 f 3
97 f I
75 f 2
<0.025
N.S.
N.S.
<0.005
<0.005
<0.005
TABLE3. Renin-aldosterone profile
Results are means 2 SEM. Significances of comparisons between normotensive (control)
and hypertensive subjects are shown. N.S.,Not significant.
Plasma renin activity (ng h-l
Recumbent
Before saline infusion
ARer saline infusion
Before frusemide
ARer frusemide
Plasma aldosterone (ng/dl)
Recumbent
Before saline infusion
ARer saline infusion
Before frusemide
After frusemide
Control
subjects (n = 30)
Hypertensive
subjects (n = 30)
P
1.27 f 0.28
5 . 6 2 f 0.76
0 . 7 2 f 0.07
2.32 f 0 . 3 2
18.88 f 2.39
0.94 f 0.06
5.12 f 0.88
0.82 f 0.04
2.74 & 0.41
15.51 f 2.09
N.S.
10.68 ? 1.37
3 1 . 0 5 f 3.06
4.5 f 0.48
1 5 . 7 2 k 1.60
53.06 f 5.65
8.07 f 1.20
36.20 f 3.46
3.79 f 0.45
15.36 f 1.72
40.38 f 3.42
N.S.
m1-l)
analysed as either individual groups or as a
combined group (r < 0.2000, P > 0.05).
Overnight recumbent (basal) systolic and
diastolic blood pressures and heart rates of
hypertensive subjects (mean of 10 determinations) were elevated compared with those of
control subjects. Inpatient basal diastolic blood
pressure was lower than the corresponding
outpatient casual diastolic blood pressure for
most hypertensive subjects.
The only difference in the renin-aldosterone
responses between control and hypertensive subjects was the post-frusemide plasma aldosterone
(Table 3).
There were only- small differences in serum
chemistry results between control and hypertensive subjects (Table 4), and there were no
differences in urinary electrolyte excretion.
Volume characteristics
Blood volume. Erythrocyte mass in control
N.S.
N.S.
N.S.
N.S.
N.S.
N.S.
N.S.
<0.005
TABLE
4. Serum and urine chemistry profile
Results are means ? SEM. Significances of comparisons
between normotensive (control) and hypertensive subjects
are shown. N.S.,Not significant.
Serum
Glucose (mg/dl)
Urea nitrogen
(mg/dl)
Creatinine(mg/dl)
Sodium (rnmol/l)
Potassium (mmol/l)
Chloride (rnmol/l)
Total CO, content
(mmol/l)
24 h urine
Na+ (rnmol/g of
creatinine)
K+ (mmol/g of
creatinine)
CI- (mmol/g of
creatinine)
Creatinine (9)
Control
subjects
Hypertensive
subjects
P
92+ I
IS? 1
97 f 3
15 f 1
<0.05
1.1 f 0 . I
143 f I
4 . 3 f 0. I
105 f I
27 t I
1.2fO.l
142 f 0.1
4 . 2 f 0.1
104-t 1
27 f 1
<OW5
91 f 9
99 f 8
N.S.
31f3
32 ? 3
N.S.
82 t 9
101 f 8
N.S.
1.8fO.l
1.7fO.l
N.S.
N.S.
<0.05
<0.05
(0.025
N.S.
Body-jluid composition
plasma volume and the interstitial fluid, was
lower in hypertensive subjects than in control
subjects. Specifically, the ECFV was 710 ml/m2
lower in hypertensive subjects than in control
subjects, and within the ECFV it was the
interstitial fluid that principally accounted for the
reduction (560 ml/m2) in ECFV. Furthermore
the ECFV comprised a smaller portion (1.9%
less) of the total body water of hypertensive
subjects than that of control subjects. There was
no statistical differences in the mean ICFV or the
mean total body water between the control and
hypertensive subjects, although mean ICFV
comprised a larger portion of the total body
water (1 -9% more) in hypertensive subjects than
in control subjects.
and hypertensive subjects did not differ (Table 5).
In contrast, hypertensive subjects’ plasma and
total blood volumes were 150 and 170 ml/m2
lower, respectively, than those of control subjects.
Consistent with the above findings, hypertensive
subjects had 2% higher whole-body and largevessel PCV than those of control subjects.
However, the Fee,, ratio did not differ between
PUPS.
PV comprised 19% of the ECFV in both
control and hypertensive subjects. Plasma
volumes comprised a smaller portion of total
body water (0.4%) in hypertensive subjects than
in control subjects.
Extracellular and intracellular fluid volumes.
ECFV, including both the previously cited
Results
are means f
47
TABLE5. Volume characteristics
of comparisons between normotensive (control) and
SEM. Significances
hypertensive subjects are shown. N.S.,Not significant.
Control
subjects (n = 30)
Hypertensive
subjects (n = 30)
P
1.04 f 0.02
2.06 f 0.05
25.9 ? 0.66
1.02 f 0.02
1.99 f 0.04
24.33 f 0.66
N.S.
N.S.
N.S.
1.69 f 0.03
3.35 f 0.07
42.0 2 0.94
1.54 f 0.02
3.01 f 0.05
36.77 f 0.69
(0.0005
<04005
<0.0005
2.73 f 0.05
5.41 f 0.11
67.90 f 1.50
2.56 f 0.04
5 . 0 0 f 0.08
61.10f 1.25
10.01
<0.005
<0.005
7.05 f 0.16
14.01 f 0.33
175.8 f 4.06
6.49 f 0.18
12.67 f 0.38
154.3 f 4.26
<0.025
8.74 f 0.16
17.36 f 0.35
217.63 f 4.39
8.03 f 0.18
15.67 f 0.39
190.9 f 4.34
<0.005
<0.005
<0.0005
14.04 f 0.36
27.89 f 0.78
349.9 f 9.67
13.97 f 0.34
27.24 f 0.70
331.97 f 7.95
N.S.
N.S.
N.S.
Erythrocyte mass
I/m’
I
ml/kg
Plasma volume
I/m2
I
ml/kg
Total blood volume*
Ilm’
I
ml/kg
Interstitialfluid volumet
Ilm’
I
mllkg
Extracellular fluid volume (ECFV)
I/m‘
I
ml/kg
Intracellularfluid volume$
llm2
I
mllkg
Total body water
l/m2
I
ml/kg
Whole body PCVg
Large-vessel PCV
FCd“
(Plasma volume1ECFV) x 100 (%)
(Plasma volumehotal body water) x 100 (%)
(ECFVhotal body water) x 100 (%)
22.78 f 0.38
45.25 f 0.86
567.57 f 10.7
0.38 f 0.00I
0.45 f 0.001
0.84 f 0 4 0 1
19.3
7.4
38.4
Total blood volume = erythrocyte mass + plasma volume.
t Interstitialfluid volume = ECFV - plasma volume.
$ lntracellular fluid volume = total body water - ECFV.
5 Whole-body PCV = erythrocyte massltotal blood volume.
It F,,,,
ratio = whole-body PCVIlarge-vessel PCV.
22.00 f 0.36
42.91 ? 0.80
522.9 f 8.04
0.40 f 0.001
0.47 f 0.001
0.85 f 0.001
19.2
7.0
36.5
<0.025
<0.0005
N.S.
<o.os
<0.005
<0.005
<0.005
N.S.
N.S.
<0.025
<0.05
48
J. H . Bauer and C. S . Brooks
Correlation studies
The correlation between each body-fluid space
(I/m2) and systolic and diastolic basal blood
pressure was calculated for the separate and
combined groups (control and hypertensive
subjects). For the combined groups, there were
significant correlations between diastolic blood
pressure and PV ( r = -0.420, P < 0.001) and
between systolic blood pressure and PV (r =
-0.368, P < 0.001). There were no significant
correlations between systolic or diastolic blood
pressure and plasma volume for control subjects
or hypertensive subjects when analysed
separately. No other significant correlations were
found.
Discussion
Reports in the literature on body-fluid compartment studies in hypertensive man are contradictory, probably due to variations in sex and
race, level of blood pressure and degree of
end-organ damage, diet, techniques employed,
method of expression of body-fluid volumes and
sample size. Tarazi [2] has reported that comparisons should be made only if subject populations are identical in sex and race and are
consuming similar dietary quantities of sodium
and potassium, and if investigators express
body-fluid volume data as a function of both
height and weight. From Owen’s Handbook of
Statistical Tables 181, we have determined that a
sample size of approximately 30 subjects is
needed to define a significant mean difference (a
= 0.05, = 0-20) for erythrocyte mass or PV of
0.15 litre/m2, ECFV of 0.75 h e l m 2 and total
body water of 1.75 litres/m2. It should be
emphasized that our body-fluid composition
studies were done in Caucasian male subjects
with similar weight range, surface area, reninaldosterone profile and serum and urine chemistry profile (including dietary sodium and potassium intake).
Our normal-renin hypertensive subjects had
both a decreased PV (0.15 litre/m2, 8.8%) and a
decreased total blood volume (0.17 litre/m2,
6.2%). These observations have confirmed the
reports of others 12, 9-12]. Our previous inability
[11 and that of others [13, 141 to define these
differences may have been related to insufficient
sample size and the fact that the weight range of
hypertensive subjects selected for study was
neither restricted nor matched to that of normotensive control subjects.
There was an inverse relationship between
plasma volume and diastolic or systolic blood
pressure when either systolic or diastolic blood
pressure was plotted as a continuum from
normotensive to hypertensive levels. The inverse
relationship between PV and blood pressure
could not be demonstrated for control or hypertensive subjects separately, a finding similar to
that reported by Ibsen & Leth 1101. Tarazi et al.
1151 and Julius et al. (161 have reported a
significant inverse relation between plasma
volume (expressed as ml/cm or ml/kg) and
diastolic blood pressure. However, in later work
Tarazi et al. 11 71 demonstrated this correlation
only if eight patients with an inappropriate PV
expansion were excluded from a series consisting
of 55 hypertensive men.
According to Blahd [181 and Albert 1191,
whole-body PCV denotes the average distribution of erythrocytes in the plasma throughout the
vascular system and is accurately determined by
separately measuring these two components of
blood. Large-vessel PCV is not representative of
the proportion of erythrocytes found in the total
blood volume; the discrepancy, which is expressed as the Feel, ratio, is attributed to the
relatively high plasma content of blood flowing in
small vessels (18, 191. Conditions favouring a
reduction in the cross-sectional diameter of the
vascular bed are associated with a reduced Feel,
ratio 1191. Our study demonstrated that, compared with control subjects, subjects with normalrenin hypertension have proportional increases in
both whole-body and large-vessel PCV, with
preservation of the Fcellratio. Thus the reduction
in cross/sectional diameter of the vascular bed
found in essential hypertension must be widespread and not selective as to vascular bed
diameter.
In this study there was an absolute decrease in
the interstitial fluid (0.56 litre/m2, 7.9%) and in
the ECFV (0.72 litre/m2, 8.1%) in normal-renin
hypertensive subjects compared with normotensive control subjects. PV comprised approximately 19% of the ECFV in both control and
hypertensive subjects, which was similar to our
previous findings 111. Thus our data did not
demonstrate a disturbance in the forces regulating extracellular fluid partition. The observation
that plasma volume and interstitial fluid volume
comprised 0.4 and 1.5% less, respectively, of the
total body water in normal-renin hypertensive
subjects than in that of control subjects further
supports the concept of an absolute reduction in
these volumes, rather than a redistribution in the
partition of the components of the ECFV. These
findings conflict with those of Tarazi et al. [ 151
and Ibsen & Leth [ 101 because of our associated
finding of a proportional decrease in the inter-
Body-fluid composition
stitial fluid component of the ECFV. Our
previous inability [ 11 and that of others [2, 10, 14,
15, 20-221 to demonstrate a significant decrease
in ECFV may reflect a sample size insufficient to
define a 0.75 litre/m2 difference and an unrestricted weight range of subjects selected for study.
There were no statistical differences in the
ICFV or total body water (expressed as l/mz) of
control and hypertensive subjects. However, the
ECFV comprised 1.9% less, whereas the ICFV
comprised 1.9% more, of the total body water in
hypertensive subjects than in control subjects.
These observations differ from our earlier observation 11 that there was a 1 5 litres/m2 absolute
increase in the ICFV of normal-renin hypertensive patients compared with normotensive
control subjects. The differences between corresponding relationships of ECFV and ICFV to
total body water of normotensive control and
hypertensive subjects are small, such that results
between different studies could be attributed to
sampling size and sampling variations. Hypertensive patients’ absolute ECFV and ICFV, if
abnormal, are not very abnormal, suggesting that
the hypertensive state is not characterized by a
major disturbance in the partition of total body
water.
We conclude that, compared with normotensive male Caucasian control subjects, male
Caucasian subjects with mild-to-moderate
normal-renin essential hypertension and minimal
end-organ damage have contracted plasma and
interstitial fluid volumes. There is no evidence for
a disturbance in the partition of the extracellular
fluid compartment.
-
Acknowledgments
We express our appreciation to James Kohrs,
Fred Rosen and Ronald Carey for technical
assistance, to the clinical Research Center staff
and Rebecca Burch for nursing support, and to
Velma Henthorne for secretarial skills. This work
was supported in part by the Medical Research
Service of the Veterans Administration and by
General Clinical Research Grant no. RR00287
04,U.S.Public Health Service.
References
111 BAUER,J.H.& BROOKS,
C.S. (1979) Volume studies in men
with mild to moderate hypertension. American Journal of
Cardiology, 44.1 163- 1 170.
49
121 TARAZI,R.C. (1976) Hemodynamic role of extracellular fluid
in hypertension. Circulation Research, 38 (Suppl. 2), 73-83.
131 BAUER, J.H., WILLIS,L.R., BURT,R.W. & GRIM, C.E. (1975)
Volume studies. 11. Simultaneous determination of plasma
volume, red cell mass, extracellular fluid, and total body water
before and after volume expansion in dog and man. Journal of
Laboratory and Clinical Medicine, 86,1009-IO17.
141 COHEN,E.L., GRIM, C.E., CONN,J.W., BLOUGH, W.M.,
GUYER,R.B., KEM,D.C. & LUCAS,C.P. (1971) Accurate and
rapid measurement of plasma renin activity by radioimmunoassay. Journal of Laboratory and Clinical Medicine,
77,1025-1038.
151 ITO, I., WOO, J., HANING,R. & HORTON,R. (1972) A
radioimmunoassay for aldosterone in human peripheral
plasma including a comparison of alternative techniques.
Journal of Clinical Endocrinology, 34,106-1 12.
161 GRIM,C.E., WEINBEROER,
M.H., HIOOINS,J.T.& KRAMER,
N.J. (1977) Diagnosis of secondary forms of hypertension.
Journal of the American Medical Association, 237, 13311335.
171 DU BOIS,D. & Du BOIS,E.F. (1916) A formula to estimate
the approximate surface area if height and weight are known.
Archives of Internal Medicine, 17,863-871,
181 OWEN,D.B. (1962) Handbook of Statistical Tables, p. 42.
Addison-Wesley Publishing Co., Massachusetts.
191 TARAZI,R.C., FROHLICH,E.D. & DUSTAN,H.P. (1968)
Plasma volume in men with essential hypertension. New
England Journal of Medicine, 278,762-765.
I101 IBSEN, H. & LETH, A. (1973) Plasma volume and exuaffiUular fluid volume in essential hypertension. Acfa Medica
Scandinavica, 19493-96.
1 I 1 I PARVINO,
H. & GYNTELBERG,
F. (1973) Transcapillary escape
rate of albumin and plasma volume in essential hypertension.
Circulation Research, 32,643-65 1.
1121 ULRYCH,M. (1973) Plasma volume decrease and elevated
Evans Blue disappearance rate in essential hypertension.
Clinical Science and Molecular Medicine, 45, 173- 18 1.
I131 WEIDMAN,
P., HIRSCH,D., BER~ITA-PICCOLI,
C., REUBI,F.C.
& ZEIGLER,
W.H. (1977) Interrelations among blood pressure,
blood volume, plasma renin activity and urinary catecholamines in benign essential hypertension. American Journal
of Medicine, 62,209-218.
1141 SCHALEKAMP,
M.A., BEEVERS,
D.G., KOLSTERS,
G., LEBEL,
M.,FRASER, R. & BIRKENHAGER, W.H. (1974) Body fluid
volume in low renin hypertension. Lancet, ii, 3 10-3 11.
1151 TARAZI, R.C., DUSTAN,H.P. & FROHLICH,E.D. (1969)
Relation of plasma to interstitial fluid volume in essential
hypertension. Circulation, 10,357-365.
1161 JULIUS,S.,PASCUAL,
A.V., REILLY,K. & LONDON,R. (1971)
Abnormalities of plasma volume in borderline hypertension.
Archives of Internal Medicine, 127,116-1 19.
171 TAW, R.C., DUSTAN,H.P., FROHLICH,
E.D., GIFFORD,
R.W. & HOFFMAN,
B.O. (1970) Plasma volume and chronic
hypertension.Archives of Internal Medicine, 125.835-842.
I181 BLAHD,W.H. (1971) Nuclear Medicine, 2nd edn, p. 595.
McGraw-Hill,New York.
I191 ALBERT,
S.N. (1971) Blood Volume and Extracellular Fluid
Volume 2nd edn, p. 48, Charles C. Thomas, Springfield,
Illinois.
1201 HOLLANDER,
W., CHOBANIAN,
A.V. & BURROWS,B.A. (1961)
Body fluid and electrolyte composition in arterial hypertension. 1. Studies in essential renal and malignant hypertension. Journal of Clinical Investigation, 40.408415.
1211 DEGRAEFF, J. (1957) lnulin space and total exchangeable
sodium in patients with essential hypertension. Acla Medica
Scandinavica, 156,337-350.
1221 ISHII, M. & Omo, K. (1977) Comparison of body fluid
volumes, plasma renin activity, hemodynamics and pressor
responsiveness between juvenile and aged patients with
essential hypertension. Japanese Circulation Journal, 41,
237-246.