Antihypertensive Properties of Furosemide
By MICHAEL DAVIDOV, M.D., NIKOs KAKAVIATOS, M.D.,
AND FRANK A. FINNERTY, JR., M.D.
SUMMARY
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The antihypertensive properties of single doses of furosemide were evaluated in 113
patients. Doses over 120 mg consistently produced a fall in arterial pressure whereas
smaller doses did not. Thus 20 of 22 patients (90%) who received more than 120 mg
had a 26 + 6% average reduction in mean arterial pressure. The hypotensive action began in 30 to 45 minutes, the nadir of the decrease occurred between 2 and 2X hours, and
the hypotension usually lasted 10 to 12 hours. Repeated weekly doses of furosemide over
a 2-month period in six patients were not associated with development of drug resistance. The antihypertensive properties of doses of furosemide of more than 120 mg
seemed to be of about the same potency as ethacrynic acid. The antihypertensive effect
of high doses of furosemide did not seem to be related to the diuretic effect or to the
decrease in plasma volume.
These studies have demonstrated that doses of furosemide of more than 120 mg consistently decreased arterial pressure. The usefulness of this agent in the long-term management of hypertension remains to be determined.
Additional Indexing Words:
Ethacrynic acid
Plasma volume
would make it a unique saluretic agent. The
present study was undertaken, therefore, to
evaluate the antihypertensive properties of
furosemide.
PREVIOUS STUDIES from this laboratory
have shown that furosemide is a potent,
rapidly acting diuretic which is effective both
parenterally and orally.1 Its potency and type
of activity seemed to depend on the dosage
used. Thus, the diuresis following doses of
40 to 60 mg was similar to that noted following
thiazides, whereas the diuresis following doses
of 100 mg and above was similar to that
following ethacrynic acid. Furosemide was
found to be particularly useful in the treatment of patients with severe congestive heart
failure who had become refractory to both
thiazides and organomercurial diuretics. After
these patients had become free of edema,
large doses of furosemide were frequently
followed by significant reductions in arterial
pressure. These observations suggested that
furosemide might have antihypertensive properties separate from its diuretic effect which
Methods
The patients were selected from the medical
wards and hypertensive clinic of the District
of Columbia General Hospital. One hundred
thirteen hypertensive patients were studied; 40
were males and 73 were females. Each of the
patients had objective evidence of vascular disease. Ophthalmoscopic examination revealed arteriovenous nicking in 104 patients and arteriovenous nicking plus retinopathy in 14 patients.
The heart was enlarged in 96 patients. None of
the patients was in congestive heart failure. There
was electrocardiographic evidence of left ventricular hypertrophy in 92, bundle-branch block
in 64, and subendocardial ischemia in six. In
order to separate the diuretic from the antihypertensive effect, patients with any evidence of
edema were excluded.
The effect of single administrations of furosemide was evaluated in 107 patients. Each of
these patients had received antihypertensive therapy including diuretics, which was discontinued
at least 7 days prior to administration of furosemide. Furosemide was supplied in 2-ml ampules
From the Department of Medicine, Georgetown
University School of Medicine and the Georgetown
University Medical Division, District of Columbia
General Hospital, Washington, District of Columbia.
Circulation, Volume XXXVI, July 1967
Sodium depletion
125
126
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in a concentration of 10 mg/ml and was administered undiluted intravenously in doses of 40
mg to 21 patients, 60 mg to 19 patients, 80 mg
to 22 patients, 100 mg to 23 patients, and in
120 to 300 mg to 22 patients.
In order to determine whether repeated doses
of furosemide were associated with drug resistance or tachyphylaxis, furosemide was administered at weekly intervals to six randomly selected patients with mild hypertensive vascular
disease. Previous therapy (0.25 mg of reserpine
plus 100 mg of hydrochlorothiazide) had been
discontinued 6 weeks before administration of
furosemide. Furosemide was injected in weekly
doses of 100 to 160 mg per injection for 8 weeks.
For 3 weeks before and 3 weeks following the
furosemide therapy, a placebo was injected intravenously once a week.
Patients arrived in the cardiovascular laboratory in the fasting state and were weighed before
administration of furosemide and at 2, 8, 24,
and 48 hours following injection. In the single
dose studies, the arterial pressure was recorded
at 10-minute intervals by the auscultatory method
with patients in the supine position. At the beginning and end of the period of observation,
the arterial pressure was also recorded with patients in the sitting and standing positions. During the 14-week period of observation when
furosemide was administered at weekly intervals,
the arterial pressure was recorded daily. The
mean arterial pressure was calculated as the
arithmetic mean (systolic plus diastolic divided
by two). The control arterial pressure represented
the average of five determinations after the arterial pressure was stabilized. The per cent decreases represented the averaged percentages.
Urine was collected through an indwelling
catheter at 30-minute intervals during the control period of 3 to 4 hours and 15, 30, 60,
120, and 180 minutes following the dose of
furosemide. Urinary sodium and potassium were
determined photometrically by the method of
Berry and associates.2 Values were expressed as
uEq per minute. The control value represented
the average of at least three determinations obtained during the control period when the electrolyte excretion was fairly stable.
The hematocrit was measured in Wintrobe
tubes on blood obtained without stasis from the
antecubital vein. Serum sodium and potassium,2
uric acid,3 blood glucose,4 alkaline phosphatase,5 6 serum glutamic oxalacetic transaminase,7
and total protein and albumin8 were determined
by standard methods. These determinations were
performed immediately prior to, and 2, 24, and
48 hours after, administration of furosemide.
Plasma volume was determined in five patients. Following collection of a blank sample,
DAVIDOV ET AL.
50pc of 13I1- HSA* was injected during a
period of 3 seconds into the antecubital vein
through a 14-gauge needle from an in vitro
calibrated syringe. Samples were obtained at 20,
25, 30, 35, and 40 minutes after administration
of indicator from the antecubital vein of the
opposite arm and collected in tubes containing
dried heparin. The radioactivity of the samples
was determined in a scintillation well counter.t
The plasma volume was calibrated by extrapolating the radioactivity to the time of injection.
Counts per sec and per milliliter of indicator
were plotted on the ordinate, and the times in
minutes on the abscissa of semilogarithmic paper.
The integral of the indicator-dilution curves was
determined according to the method of Lilienfield and Kovach.9 Total blood volume was calculated from the formula:
Total blood volume =
plasma volume
I - (peripheral hematocrit x 0.91 x 0.96)
and red cell volume from the formula: RCV=
TBV - PV.
Cardiac output was determined in nine patients. Diuretics had been withheld from these
patients for 7 days prior to and during the entire
study. Serial relative changes in the cardiac output were determined by the dye-dilution method
using Coomassie Bluet as indicator, a photoelectric earpiece, and a Mark II Cambridge Dye
Recorder with a high resistance input circuit.
They were expressed in arbitrary units derived
from the reciprocal of the area under the recorded curve.10
The total peripheral resistance was also expressed in arbitrary units from the formula:
Total peripheral resistance equals mean arterial
pressure divided by cardiac output. The arterial
pressure was recorded by the auscultatory
method. The mean arterial pressure was determined by the formula: Systolic plus diastolic
pressure divided by two.
The potency of varying intravenous versus
oral doses of furosemide was compared in 16
patients. Eight patients received the intravenous
preparation initially and the others received the
oral preparation initially. An interim of 7 to 10
days separated administrations. The potency of
furosemide and ethacrynic acid was compared
in 26 patients. Sixteen patients received both
drugs orally, and 10 patients received both drugs
intravenously. Half the patients received furosemide initially and half received ethacrynic acid
*Squibb radioiodinated serum albumin.
tNuclear Instrument and Chemical Corporation,
Chicago, Illinois.
::Supplied as AY-58112 by Ayerst Laboratories, Inc.,
New York, New York.
Circulation, Volume XXXVI, July 1967
FUROSEMIDE
127
Table 1
Effect of Furosemide on Weight and Mean Arterial Pressure (MAP) in 107 Patients
Dose
(mg)
No. of
patients
Control
Weight
(lb)
40
Changes
2 Hr
24 Hr
Changes
1.7
178
52
170
40
-7
1.7
171
40
-6
(mm Hg)
146
14
136
48
-7
4%
140
59
-4± 2%
Weight
(lb)
182
36
176
33
-6
1.4
177
54
-5
21
MAP
60
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80
100
20
19
MAP
(mm Hg)
148±21
137±49
-6±3%
144±62
-3± 2%
Weight
(lb)
182±36
176±40
-6±2
179±40
-3± 2
MAP
(mm Hg)
145 27
131
Weight
(lb)
181±47
178±51
(mm Hg)
149±16
Weight
(lb)
181±40
22
30
-6± 4%
-3±1.4
179±54
-2± 1.7
121±22
-19±5%
132±29
-11± 6%
177±42
-4±2
178±51
-3± 2
24
-10
3%
136
23
MAP
120 to 300
(Av dose,
210 + 74 mg)
22
MAP
(mm Hg)
152
18
initially. Seven to 10 days separated administration of the drugs.
Results
The effect of single intravenous administrations of furosemide on the weight and arterial
pressure in 107 patients is presented in table
1. Two hours after administration of furosemide there was always a decrease in body
weight. The decrease in weight did not seem
to be related to the dose of furosemide since
decrease in weight was greater in those patients who received doses of furosemide of
less than 100 mg than in those who received
higher doses. The effect of furosemide on
arterial pressure, however, seemed to be dose
related. A consistent reduction in arterial
pressure occurred only when furosemide was
administered in doses in excess of 120 mg.
Thus, only 21 of the 62 patients (33%) who
Circulation, Volume XXXV1, july 1967
113
21
-26
6%
121
26
-20± 9%
received furosemide in doses under 100 mg
had more than a 15% fall in arterial pressure,
whereas 20 of the 22 patients (90%) who
received doses of furosemide of 120 mg or
more had a greater than 15% average fall in
arterial pressure. The average fall in arterial
pressure in these 22 patients was 26 + 6%.
The hypotensive action began from 30 to 45
minutes after the dose, the maximal fall occurred between 2 and 2%2 hours after it, and
the hypotension usually lasted between 10
and 12 hours. In 20 of the 59 patients (34%)
who had an average fall in arterial pressure
of more than 15%, a further reduction was
noted 24 hours after administration of furosemide.
The effect of repeated weekly administrations of furosemide on the arterial pressure
in the six patients studied can be noted in
DAVIDOV ET AL.
128
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figure 1. During the placebo period, the mean
arterial pressure fell from an average of 140
26 mm Hg to an average of 128 41 mm
Hg (10 6%). After each injection of furosemide there was a fall in arterial pressure
beginning 3k to 1 hour after administration
which gradually reached its nadir in 24 to 26
hours. In these patients, the fall in blood pressure lasted 332 to 4 days and reached control
or near control levels by the fifth day. Twentyfour hours after the third injection of furosemide, the average mean arterial pressure had
fallen to 100 18 mm Hg, a 24 9% reduction.
Following the third injection, the duration of
the hypotensive effect became longer as evidenced by the sustained lower level of arterial pressure on the seventh day. The diastolic pressure had been reduced more than
15 mm Hg in each patient. Resistance or
m
:19
E
200
-
Placebo
Furosemide
P l; c
t
E
--l
t
t
t
t
t
tPlacebo
t t
t
150
100
t
50
2
3
4
5
6
7
8
9
10
11
12
14
13
WEEKS
Figure
1
The effect of repeated injections of furosemide
arterial pressure in six hypertensive patients.
on
tachyphylaxis was not observed during the
2-month period of study. The arterial pressure
gradually rose to near control levels during
the second placebo period.
Data on the urinary output and electrolyte
excretion following furosemide in 63 hypertensive patients are presented in table 2. The
onset of diuresis occurred within 1 to 2 minutes, and the peak of diuretic action seemed
to be 25 to 30 minutes. Regardless of the
dosage, natriuresis was constantly greater
than kaliuresis, potassium excretion paralleled
urinary output, and the sodium-potassium
excretion ratio was consistently increased. The
increase in urinary output and excretion of
sodium were as great following low doses of
furosemide as it was following high doses,
whereas the magnitude of potassium excretion
appeared to be greater following high doses
of furosemide. This greater kaliuresis following high doses of furosemide was reflected
by a lower sodium-potassium ratio as compared to that following lower doses of furosemide.
The changes in plasma volume, red cell
volume, and mean arterial pressure in 32
patients 2 hours after administration of furosemide are presented in table 3. In the 12
patients whose arterial pressure did not fall,
there was a 15.6 + 8% average decrease in
plasma volume whereas in the 20 patients
whose mean arterial pressure fell an average
Table 2
Effect of Furosemide on Urinary Output and Electrolyte Excretion of Sixty-three patients
Control
Urinary
output
(ml/min)
Sodium
excretion
(MAEq/min)
Potassium
excretion
1.9
Tests on 41 patients
Time after dose of 40 to
100 mg (av 63 L 19 mg)
15
30
60
min
min
min
120
min
Control
20.3
7.1
1.6
24.3
16.1
Tests on 22 patients
Time after dose of 120 to
300 mg (av 210 ± 74 mg)
15
30
60
min
min
min
16.7
21.2
14.6
4.6
247
2761
2965
2243
906
239
2080
2833
1820
739
41
188
180
122
62
34
195
201
166
91
(A,Eq/min)
Na/K
excretion
ratio
120
min
6.0
14.7
16.5
18.3
14.6
7.0
10.7
14.1
Circulation, Volume
11.0
8.1
XXXVI, July 1967
FUROSEMIDE
129
Table 3
Effect of Furosemide on Plasma Volume, Red Cell Volume, and Mean Arterial Pressure in Thirty-two
Patients
Red cell volume
Plasma volume
(ml)
(ml)
No.
Control
1
2
3
4
3879
3675
3315
3236
4308
3772
3008
3442
3072
3629
3822
3935
3591
±386
5
6
7
8
9
10
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11
12
Av
SD
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
Av
SD
3209
3679
3536
5165
2624
3022
4286
6853
2237
2864
3157
2536
2391
3452
3236
3212
3283
2810
3674
4966
3510
±+1067
2 Hr
% Change
Control
2 Hr
% Change
Twelve Patients without Fall in Arterial Pressure*
+3
2484
2418
-29
2754
+5
1705
1630
-9
3370
+2
2609
2559
-9
3027
+7
1982
1858
-15
2749
+5
3276
3427
-10
3893
+4
2988
2869
-14
3237
+7
2540
-5
2379
2860
+6
-9
1694
1590
3123
+5
-14
2549
2429
2626
+3
1598
-29
1551
2579
+6
2046
1921
3080
-19
+2
1926
1970
-25
2967
+4.6
2299
-15.6
2201
3022
+1.7
+563
+8
+365
+546
Twenty Patients with Fall in Arterial Pressuret
-9
1609
-13
2801
1772
-8
2200
2381
3130
-15
-24
-14
2675
1533
1780
-17
-23
2475
3970
2966
-11
-17
2086
2342
2175
-12
1528
-14
1735
2355
-17
2689
3260
3028
-29
-9
1965
-14
5907
2164
-1
1431
-10
2035
1452
-4
1851
-12
1935
2531
-2
2014
-13
2050
2754
-1
2038
-4
2056
2431
-10
-2
1430
2358
1590
-7
1723
-11
3067
1854
0
1857
2749
-15
1858
-8
1520
-15
1660
2724
-7
1829
-20
2626
1975
-12
1601
-21
1820
2218
-8
2201
2381
3130
-15
-14
2258
-20
3980
2623
-8.5
1892
2083
2932
-15.3
+354
S5
+6.2
+461
±870
Mean arterial pressure
(mm Hg)
% Change
2 Hr
Control
130
110
130
110
125
140
125
140
120
150
145
170
160
160
115
150
145
170
155
160
145
165
142
+19
145
165
143
±19
145
95
185
140
140
170
140
130
160
140
170
135
160
140
130
155
155
140
130
140
140
170
148
+16
100
140
105
95
140
115
135
110
120
120
100
140
110
105
130
100
140
118
+17
0
0
0
0
+4
0
0
0
+3
0
0
0
+0.6
+4
-22
-32
-29
-17
-25
-27
-12
-18
-18
-18
-25
-14
-23
-21
-10
-21
-19
-7
-29
-17
-20
+6
*Net loss of plasma volume = 569 ± 300 ml, and net gain of red cell volume = 99 ± 40 ml.
tNet loss of plasma volume = 577 ± 265 ml, and net loss of red cell volume = 191 ± 147 ml.
of 20±6%, there was a 15.3+6% decrease in
plasma volume. Although the plasma volume
following furosemide was consistently reduced
whether the arterial pressure was reduced or
not, the red cell volume was decreased only
when the arterial pressure fell.
Serial determinations of plasma volume in
six patients demonstrated that the plasma
Circulation, Volume XXXVI, JIly 1967
volume returned to control values 48 hours
after administration of furosemide, whereas
the arterial pressure remained reduced (table
4). No consistent changes were observed in
the cardiac output 2 hours following furosemide. In three patients there was no change,
whereas in six patients there was an average
increase of 17 ± 5%. On the other hand the
130
DAVIDOV ET AL.
Table 4
Serial Determination of Plasma Volume, Red Cell Volume, and Arterial Pressure
Following 100 mg of Furosemide in Six Patients
Mean arterial pressure
(mm Hg)
Plasma volume
(ml)
Red cell volume
(ml)
Control
2 Hr
150
130
-13
120
-20
120
3772
3237
-14
3384
-10
3793
+0.5
2869
2795
-3
2801
-2
2885
+0.6
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
total peripheral resistance decreased in every
patient by an average of 24 ± 3%.
The effects of intravenous and oral furosemide on the arterial pressure and weight are
compared in table 5. No significant difference
was noted between the oral and intravenous
routes of administration. Again doses under
100 mg were not consistently followed by a
fall in arterial pressure whereas doses over
120 mg whether administered intravenously
or orally were.
Tables 6 and 7 demonstrate that single
intravenous and oral administrations of furosemide and ethacrynic acid exert similar
diuretic and antihypertensive responses. The
serum electrolytes and blood chemical
changes 2 hours following furosemide can
be seen in table 8.
Discussion
The data presented suggest that intravenous doses of furosemide over 120 mg consistently produce a fall in arterial pressure
whereas smaller doses do not. Thus, only 21
of 62 patients who received less than 100 mg
of furosemide had more than a 15% average
fall in arterial pressure, whereas 20 of 22
who received more than 120 mg had more
than a 15% average reduction.
The antihypertensive effect of high doses
of furosemide did not seem to be secondary
to or related to its diuretic effect. None of
the patients studied showed any evidence of
clinical edema. Although loss of weight, increase in urinary volume and urinary sodium
and potassium, and a decrease in plasma
volume consistently followed each administration of furosemide, no direct relation was
noted between any of these parameters and
% Change
24 Hr % Change
48 Hr
% Change
-20
the fall in arterial pressure. Thus, the average
loss of weight following doses of furosemide
above 120 mg was actually less than that
observed after 40 mg of furosemide (table 1).
The urinary output and the urinary excretion
of sodium were similar whether the dose of
furosemide was under 100 mg or above (table
2). Although the plasma volume was consistently decreased following furosemide, the
average decrease in plasma volume was similar in those patients whose arterial pressure
did not fall as in those whose arterial pressure did fall (table 3).
The mechanism of the antihypertensive activity of high doses of furosemide remains
unknown. The cardiac output 2 hours following furosemide was either unchanged or increased. The total peripheral resistance, however, was consistently decreased. It is
interesting that although the plasma volume
decreased whether the arterial pressure fell
or not, the red cell volume fell only when
the arterial pressure was reduced. The significance of the latter finding is not known.
Current studies in our laboratory have shown
that replacement of the plasma volume with
dextran following furosemide has no effect
on the arterial pressure. These data suggest
that the antihypertensive effect of high doses
of furosemide is separate from its effect on
plasma volume.
In the six patients so studied, repeated
injections of furosemide were not associated
with the development of resistance at least
during the 2-month period of observation.
Although the fall in arterial pressure during
the drug period exceeded that during the
two placebo periods (fig. 1), the value of
Circulation, Volume XXXVI, July 1967
FUROSEMIDE
131
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Circulation, Volume XXXVI, July 1967
133
FUROSEMIDE
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furosemide as an antihypertensive agent remains to be established. It should be emphasized that these six patients were suffering
from only mild hypertension. The same control of arterial pressure had previously been
accomplished by the daily oral administration
of reserpine and a thiazide diuretic.
It would seem that high doses of furosemide
have a greater effect on the arterial pressure
than any dose of the thiazides. The optimum
fall in arterial pressure in nonedematous patients following thiazides varies between 12
to 15%.11-13 The average fall in arterial pressure following higher doses of furosemide in
this study was 26±6%. Most investigators
would agree that once the optimum dose of
thiazides has been administered (for example,
500 mg of chlorothiazide or 50 mg of hydrochlorothiazide administered twice daily),
increasing the dose does not increase the antihypertensive activity.14' 15 Whether furosemide is simply a more potent thiazide and
exerts a greater antihypertensive effect because
of its particular dose response curve
or whether the mechanism of its antihypertensive action is entirely different from that
of thiazides is not entirely clear.
It would also seem from the data presented
that orally administered furosemide (single
administration) is as potent as intravenously
administered furosemide (table 5) and that
furosemide has about the same potency as
ethacrynic acid (tables 6 and 7). Thus,
furosemide given orally or intravenously in
doses of less than 100 mg does not produce
significant changes in arterial pressure whereas doses over 120 mg administered by either
route are followed by falls in arterial pressure
of 17 and 21%, respectively (table 5).
No side effects were noted following administration of furosemide. Previous studies
have demonstrated that even when large
doses of furosemide were administered to
patients with renal insufficiency, electrolyte
abnormalities did not occur.' Unlike other
diuretic agents, increased kaliuresis did not
occur in the absence of excessive diuresis.1 16
Although these and previous studies have
shown that there were no significant changes
DAVIDOV ET AL.
134
Table 8
Effect of Furosemide on Serum Sodium and Potassium, Glucose, SGOT, Alkaline
Phosphatase, Total Protein, Albumin, Blood Urea Nitrogen and Uric Acid in Seventy-five
Patients
Sodium (mEq/L)
Potassium (mEq/L)
Glucose (mg%)
Alkaline phosphatase*
Total protein (g)
Albumin (g)
SGOTt
Blood urea nitrogen (mg%)
Uric acid (mg%)
*Klein-Babson-Reid
Control
2 Hr
134 3
4.2 ± 0.4
88 31
1.6 ± 0.4
6.9 ± 1.4
140 ±4
4.0 ± 0.5
86 35
1.4 ± 0.3
7.4 ± 0.2
4.3±1.2
17±3
17 ± 11
6.4 ± 1.7
4.0±1.6
17±2
17 ± 11
5.8 ± 1.5
units.
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
tBabson units.
in the blood chemistry and in renal or hepatic
function following furosemide, excessive diuresis with a rapid depletion in plasma volume
has occasionally followed relatively small
doses of furosemide. Thus, a profound diuresis
(more than 3 L of urine in 3 hours) has
followed a small dose (40 mg) in a patient
who had not previously received diuretics.
In order to avoid this possibility, therefore,
it is recommended that furosemide therapy
be initiated in a dosage of 40 mg. If excessive
diuresis does not occur, the dose may be
doubled and then tripled in a period of 24 to
48 hours. Once a dosage of 120 mg has been
reached, it may then be repeated daily or
twice daily as the need arises. Studies are now
being carried out to determine the optimum
effective dosage and method of administration
of furosemide when given alone or in combination with other antihypertensive agents
in the long-term management of hypertension.
It is hoped that these preliminary studies
will stimulate others to evaluate the antihypertensive properties of furosemide.
4.
5.
6.
7.
8.
9.
10.
11.
References
1. DAVIDOV, M., KAKAViATOS, N., AND FINNERTY,
F. A., JR.: Intravenous furosemide in heart
failure. JAMA. In press.
2. BERRY, J. W., CHAPPELL, D. C., AND BARNEs,
R. B.: Improved method of flame photometry.
Ind Eng Chem Anal Ed 18: 19, 1946.
3. LONDON, M., AND MARYMONT, J. H., JR.: Anal-
12.
13.
yses on heat-coagulated blood and serum: I.
The determination of uric acid. Clin Chem
10: 298, 1964.
SoMOGYI, M.: Notes on sugar determination.
J Biol Chem 195: 19, 1952.
KLEIN, B., READ, P. A., AND BABSON, A. L.:
The determination of alkaline phosphatase.
Clin Chem 6: 269, 1960.
BABSON, A. L.: The determination of alkaline
phosphatase. Amer J Med Techn 26: 379,
1960.
FURANO, A., AND SHENA, A.: Adaptation of
Babson's method for the determination of
SGOT in clinical laboratory. Clin Chem 11:
23, 1965.
WELCHSELBAUM, F.: Determination of protein
by biuret method. Amer J Clin Path (Tech
Sect) 10: 40, 1946.
LILLIENFELD, L., AND KOVACH, R.: Simplified
method of calculating mean circulation time
and downslope from indicator dilution curves.
Proc Soc Exp Biol Med 91: 595, 1956.
GABE, L., AND SHILLINGFORD, J.: The photoelectric earpiece technique for recording dye
dilution curves. Brit Heart J 13: 271, 1961.
Fmis, E. D., WANKO, A., WILSON, I. M., AND
PARRISH, A. E.: Treatment of essential hypertension with chlorothiazide (Diuril). JAMA
166: 137, 1958.
FINNERTY, F. A., JR., BucHmoLz, J. H., TucKMAN, J., HAJJAR, G. T., AND MASSROARo, G. C.:
Evaluation of chlorothiazide alone in the
treatment of moderately severe and severe
hypertension. Circulation 20: 1037, 1959.
HOLLANDER, W., AND WILKuNs, R. W.: ChloroCinculation, Volume XXXVI, Jaly 1967
FUROSEMIDE
135
thiazide: A new type of drug for the treatinent of arterial hypertension. Boston Med
Quart 8: 1, 1957.
14. MOYER, J. H.: Huinan pharm11acology of thiazide
derivatives. JAMA 170: 2048, 1959.
15. FORD, R. V., MOYER, J. H., AND SpuRR, C. L.:
Clinical and laboratory observations on chloro-
thiazide (Diuril). Arch Intern Med (Chicago)
100: 582, 1957.
16. OG)EN-, D. A., SCI-IERR, L., SPRFTz, N., AND
RUBIN, A. L.: A comparison of the properties
of chliorothiazide, spironolactone and combination of both as diuiretic agents. New Eng J
Med 265: 358, 1961.
Kt:4
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Socrates on Educators
And we must see that the Sophist in commending his wares does not deceive us, like
the wholesaler and the retailer who deal in food for the body. These people do not
know themselves which of the wares they offer is good or bad for the body, but in selling them praise all alike, and those who buy from them don't know either, unless one
of them happens to be a trainer or a doctor. So too those who take the various subjects
of knowledge from city to city, and offer them for sale retail to whoever wants them,
commend everything that they have for sale, but it may be, my dear Hippocrates, that
some of these men also are ignorant of the beneficial or harmful effects on the soul of
what they have for sale, and so too are those who buy from them, unless one of them
happens to be a physician of the soul. If then you chance to be an expert in discerning which of them is good or bad, it is safe for you to buy knowledge from Protagoras or
anyone else, but if not, take care you don't find yourself gambling dangerously with all
of you that is dearest to you. Indeed the risk you run in purchasing knowledge is much
greater than that in buying provisions.-EDITH HAMILTON and HUNTINGTON CAIRNS
(Ed.): The Collected Dialogues of Plato. Newv York, Bollingen Foundation (Pantheon
Books; Bolli-ngen Series 71) 1961, p. 313.
Circulation, Volume XXXVI, July 1967
Antihypertensive Properties of Furosemide
MICHAEL DAVIDOV, NIKOS KAKAVIATOS and FRANK A. FINNERTY, JR.
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Circulation. 1967;36:125-135
doi: 10.1161/01.CIR.36.1.125
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Copyright © 1967 American Heart Association, Inc. All rights reserved.
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