494
Vitamin E Protects Against Impairment of
Endothelium-Mediated Relaxations
in Cholesterol-Fed Rabbits
A.L. Stewart-Lee, L.A. Forster, J. Nourooz-Zadeh, G.A.A. Ferns, E.E. Angga'rd
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Abstract The vascular effects of dietary vitamin E were
investigated in isolated carotid artery preparations from cholesterol-fed New Zealand White rabbits. Rabbits were fed
either a control, 1% cholesterol, or 1% cholesterol plus 0.2%
vitamin E diet for 4 weeks. In raised-tone preparations,
relaxant responses to acetylcholine were enhanced in rabbits
fed cholesterol plus vitamin E, reversing the reduction in
responses measured in preparations from cholesterol-fed rabbits. Relaxant responses to the calcium ionophore A23187
were significantly enhanced in cholesterol plus vitamin E-fed
rabbits compared with those fed cholesterol alone, with no
difference between control and cholesterol-fed rabbits. Relaxant responses to sodium nitroprusside were not different
between the three dietary groups. Constrictor responses to
noradrenaline and serotonin in isolated carotid artery preparations at basal tone were unaltered after cholesterol and
cholesterol plus vitamin E diets. The copper-induced oxidation
of /3-very-low-density lipoprotein (/3VLDL) isolated from
plasma of rabbits fed a cholesterol plus vitamin E diet was
almost completely inhibited compared with the oxidation of
/3VLDL from rabbits fed cholesterol alone. These results show
that vitamin E prevents endothelial dysfunction associated
with cholesterol feeding and suggests that vitamin E may be
beneficial in preventing functional impairment associated with
atherosclerosis. (Arterioscler Thromb. 1994;14:494-499.)
H
Methods
Animals and Dietary Protocol
ypercholesterolemia induces endothelial dysfunction, leading to an impairment of endothelium-mediated relaxant responses. l~s This
may be a result of an attenuation in the production,
release, or bioactivity of nitric oxide-related endothelium-derived relaxing factor (EDRF). 6 Reactive oxygen
species (ROS) are known to be released from monocytes/intimal macrophages, smooth muscle cells, endothelial cells, and LDL during its modification in the
arterial wall, and it is possible that they contribute to
endothelial dysfunction, since ROS generation is increased in atherosclerotic vessels7-8 and there is evidence that ROS inactivate EDRF in vitro. 910
Vitamin E is the most abundant, naturally occurring,
lipid-soluble antioxidant in plasma. It is carried within
the low-density lipoprotein (LDL) particle and prevents
its oxidation in vitro. 1113 Low doses of vitamin E (0.2%)
do not have a significant effect on plasma cholesterol
levels14; therefore, a 1% cholesterol diet containing
0.2% vitamin E could be used to test its action as an
antioxidant agent in a model of atherogenesis. In the
present study, we have examined the possible role of
oxidative processes in the early impairment of endothelium-mediated responses by studying the effects of the
antioxidant vitamin E on endothelium-mediated relaxations in the carotid artery of the hypercholesterolemic
rabbit.
Received June 24, 1993; revision accepted December 14, 1993.
From The William Harvey Research Institute, St Bartholomew's Hospital Medical College, University of London, UK.
Correspondence to Dr A.L. Stewart-Lee, The William Harvey
Research Institute, Charterhouse Square, London EC1M 6BQ,
UK.
•
Key Words • rabbit carotid artery • hypercholesterolemia
antioxidants • vitamin E • endothelium
Male New Zealand White rabbits weighing 2.0 to 2.5 kg
were obtained at 8 to 10 weeks of age (Rosemead Rabbit Co,
Essex, UK). They were assigned to one of three dietary
groups: (1) control diet consisting of standard rabbit chow
(containing 0.003% vitamin E; Scientific Diet Services, Essex),
(2) rabbit chow containing 1% cholesterol, and (3) chow
containing 1% cholesterol and 0.2% vitamin E. (A group of
rabbits on standard chow supplemented with vitamin E was
not included in the study because of the lipophilic nature of
vitamin E, meaning that comparable levels of plasma vitamin E
could not be attained in the absence of cholesterol feeding.)
Rabbits were allowed free access to water. Cholesterol diets
were prepared by spraying a solution of cholesterol dissolved
in diethyl ether over the standard chow so as to obtain an even
distribution and drying the diet overnight to ensure complete
evaporation of the solvent. The control diet was similarly
treated with diethyl ether alone. The vitamin E diet was
prepared by mixing o-tocopherol directly into diet containing
1% cholesterol. Rabbits were maintained on their respective
diets for a period of 4 weeks.
Four milliliters of blood was collected from every animal
(via the marginal ear vein) before the start of treatment to
enable baseline cholesterol and vitamin E concentrations to be
established. Animals were killed by a lethal dose of sodium
pentobarbitone (60 mg/kg) injected into the marginal ear vein.
Blood for the measurement of cholesterol and vitamin E levels
and for the isolation of 0-very-low-density lipoprotein
OVLDL) was obtained by cardiac puncture and collected in
tubes containing citrate solution to a final concentration of
0.38% citrate.
Pharmacological Procedures
Preparation of Tissue for Pharmacology
Both left and right carotid arteries were excised and divided
into a total of six rings, each approximately 7 mm long.
Stewart-Lee et al
Vascular rings were mounted horizontally under isometric
conditions in 10-mL organ baths according to the method of
Bevan and Osher.15 The tissues were bathed in Krebs' solution
of the following composition (mmol/L): NaCl 133, KC1 4.7,
NaH2PO4 1.35, NaHCO3 16.3, MgSO4 0.61, glucose 7.8, and
CaCl2 2.52.16 The Krebs' solution was bubbled with 95%
O 2 /5% CO2 and maintained at a constant temperature of 37°C.
Preparations were allowed to equilibrate for at least 1 hour
under a predetermined optimal resting tension of approximately 2.0 g. Responses of the circular smooth muscle were
recorded by use of a Grass FT03C transducer and displayed on
an ink-writing oscillograph (Grass model 79).
Pharmacological Protocol
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Noradrenaline (0.01 to 300 fimol/L) and serotonin (0.01 to
30 jtmol/L) were added cumulatively to the bath so that
contractile concentration-response curves could be constructed. To study relaxation, vessel tone was raised by the
addition of a concentration of noradrenaline that produced
approximately 60% to 70% of the maximum contractile response in each vessel (10 jimol/L). Acetylcholine (0.1 to 100
/xmol/L), the calcium ionophore A23187 (0.1 to 30 /imol/L),
and sodium nitroprusside (0.1 to 300 janol/L) did not cause
desensitization and were therefore added cumulatively to the
bath.
At least 20 minutes was allowed between consecutive doseresponse curves, during which time the Krebs' solution was
changed every 5 minutes. All vascular rings were tested with
noradrenaline, serotonin, and acetylcholine, with three rings
being randomly selected to be tested with the calcium ionophore A23187 and the remaining three with sodium
nitroprusside.
Biochemical Procedures
Isolation of 0VLDL
Blood collected by cardiac puncture from cholesterol- and
cholesterol+vitamin E-fed rabbits at the time they were killed
was centrifuged to obtain plasma. The plasma obtained from
individual rabbits within each of the two groups was pooled
separately. /3VLDL (density < 1.006) was obtained from the
plasma by ultracentrifugation for 20 hours at 50 000 rpm at 4°C
in a Ti 70 rotor (Beckman Instruments Inc, Fullerton, Calif).
The /3VLDL layer was recovered and recentrifuged at density
1.006 for 20 hours at 50 000 rpm at 4°C. The supernatant
(/3VLDL) was collected and used for oxidation studies. Protein
content was determined by the Lowry method,17 using bovine
serum albumin as the standard, so that equivalent amounts of
/3VLDL could be used in the oxidation studies.
Oxidative Modification of &VLDL
/3VLDL was incubated at a concentration of 100 fig protein/mL in 5 /xmol/L copper sulfate solution for various time
intervals (0 to 6 hours) at 37°C. Ten microliters of 5 mmol/L
butylated hydroxytoluene was added to each tube at the end of
the set incubation times to halt the oxidation reaction.
Determination of Lipid Peroxidation
Lipid peroxidation was determined by measuring the
thiobarbituric acid-reactive substances (TBARS) in the medium. One and one half milliliters 20% trichloroacetic acid
(TCA) and 0.5 mL 0.67% thiobarbituric acid were added to
300 ML of each sample, using 0.2, 0.5, and 1.0 nmol/L
malondialdehyde (MDA) as a standard. After boiling for 60
minutes, MDA-like compounds in each sample were extracted
into 2 mL butanol, and the fluorescence was measured with a
Perkin-Elmer fluorometer with excitation at 515 nm and
emission at 553 nm.
Vitamin E in Hypercholesterolemia
495
Determination of Serum Cholesterol Levels
Two-milliliter blood samples obtained both at the start of
treatment and when the rabbits were killed were immediately
centrifuged, and the serum was removed. Serum cholesterol
levels were estimated by use of an automated system (Vitalab
100, Vital Scientific Ltd, Sussex, UK) by an enzymatic-colorimetric method. 1820
Determination of Serum Vitamin E Levels
Lipid Extraction
Serum (50 /xL) was transferred into a glass test tube, and
vitamin E acetate (8 ^g in 100 /xL ethanol) was added as
internal standard. Ethanol (400 /nL), isooctane (800 fiL), and
water (500 fiL) were then added sequentially. The sample was
vortexed for 15 seconds and was then centrifuged for 5 minutes
at 5000 rpm. The organic phase (upper layer) was transferred
into a screw-cap vial, and the solvent was removed under
nitrogen. The residue was dissolved in acetonitrile (100 /ML),
and 25 ^L of the sample was used for the analysis.
High-Performance Liquid Chromatography
The system consisted of a model L-6200 pump (Hitachi Ltd,
Tokyo, Japan), a Rheodyne injector (model 7010) equipped
with a 20-/iL sampling loop (Rheodyne Inc, Cotati, Calif), and
a model 440 UV spectrophotometer (Waters Associates Inc,
Milford, Mass). The separation was carried out on a Hypersil
ODS (3x100 mm, particle size 5 ^im, Chrompack, Middelburg,
the Netherlands) using acetonitrile/water/tetrahydrofuran (80/
6/14, vol/vol/vol). A flow rate of 0.7 mL/min was used. Absorbance was monitored at 280 nm.
Histological Procedures
After the pharmacological study, vessel segments were
carefully removed from the organ baths and dismounted from
the hooks. Two vessel segments were placed in 4% paraformaldehyde solution and later stained with 0.25% AgNo3
solution to establish the integrity of the endothelium. Two
further segments were stained for lipid with oil red O. The two
remaining segments were gently blotted to remove excess
Krebs' solution and then weighed, and their lengths were
measured to determine the average wet weight per unit length.
Two rabbits from each of the three dietary groups were
perfusion-fixed with 4% paraformaldehyde as previously described,21 and segments of carotid artery were prepared for
scanning and transmission electron microscopy.21
Drugs
Cholesterol and MDA were obtained from Aldrich Chemical Co, Gillingham, Dorset, UK. Vitamin E [(±)-o-tocopherol
acetate], noradrenaline bitartrate, 5-hydroxytryptamine creatinine sulfate (serotonin), acetylcholine chloride, the calcium
ionophore A23187, sodium nitroprusside, bovine serum albumin (fraction V), 2-thiobarbituric acid, citric acid (trisodium
salt), and butylated hydroxytoluene were all obtained from
Sigma Chemical Co, Poole, UK. All Krebs' drugs and butanol
(butan-1-ol) were obtained from BDH Lab Supplies, Poole.
Sodium pentobarbitone was obtained from RMB Animal
Health Ltd, Dagenham, UK. Noradrenaline and serotonin
were made up fresh each day, both being dissolved in distilled
water. Sodium nitroprusside was protected from light. The
calcium ionophore A23187 was dissolved in dimethyl sulfoxide
(DMSO), being stored at -20°C at concentrations of 5, 6, and
7 ^imol/L in aliquots each containing approximately 100 /xL,
which were defrosted only once and used immediately.
Treatment of Results and Statistical Methods
Contractions to noradrenaline and serotonin are expressed
in grams. Relaxations to acetylcholine, the calcium ionophore
A23187, and sodium nitroprusside are expressed as a percentage of the raised-tone preparations. For each result, one
496
Arteriosclerosis and Thrombosis
Vol 14, No 3 March 1994
Body Weights and Serum Cholesterol Concentrations at the Time Rabbits Were Killed
and Vessel Segment Weights After Pharmacological Investigations
Body Weight,
kg
Serum Cholesterol,
mmol/L
Segment Weight,
mg/mm
Group 1
3.0±0.1 (10)
2.1+0.1 (8)
1.9±0.1 (10)
Group 2
3.2±0.1 (12)
2.0+0.1 (10)
29.4±2.7(12)*
Group 3
3.1 ±0.1 (10)
2.0±0.2 (8)
29.3±0.2(10)*
All values are given as mean±SEM, with the number of observations (n) in parentheses. Group 1,
control diet; group 2, 1% cholesterol diet; and group 3, 1% cholesterol plus 0.2% vitamin E diet.
Signrficant differences were calculated by analysis of variance (ANOVA) followed by post hoc tests
when ANOVA indicated signrficant variation between the three groups. *Significant difference of
P<.001 compared with group 1.
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average value per animal was taken. In the figure legends, n
refers to the number of animals from which vessels were used.
Statistical analysis of results within the three groups was
performed with one-way ANOVA, applying the Bonferroni
method when ANOVA indicated a significant difference between the groups. A probability of P<.05 was considered
significant. Statistical analysis of results was performed on a
Dell 316SX PC using GraphPAD INSTAT software. For the
measurement of lipid peroxidation by TBARS, duplicate determinations were carried out and the average values expressed in terms of MDA equivalents (nmol MDA equivalents
per milliliter of sample).
Results
Body and Vessel Segment Weights
There was no significant difference in either body
weights or the wet weight of vessel segments between
the three different groups of rabbits (Table).
Serum Cholesterol and Vitamin E
The average baseline serum cholesterol level at the
start of the dietary regimen was 1.9±0.1 mmol/L. Serum
cholesterol levels were significantly greater at the time
of death in the cholesterol-fed rabbits, whether or not
they received vitamin E supplementation (Table).
Mean average baseline serum vitamin E levels were
2.3 ±0.8 /ig/mL. After 4 weeks of a cholesterol diet
enriched with vitamin E, vitamin E levels rose significantly, to 76.8±10.4 /ig/mL (P<.001).
Pharmacology
Acetylcholine, A23187, and sodium nitroprusside
produced dose-dependent relaxant responses in all
raised-tone preparations of the rabbit carotid artery
tested. Relaxant responses to acetylcholine in preparations from cholesterol-fed rabbits were significantly
reduced compared with rabbits fed the control diet at
0.3, 1.0, and 3.0 /xmol/L acetylcholine (Fig 1). Relaxant
responses measured in preparations from cholesterol
plus vitamin E-fed rabbits were significantly greater
than in those from cholesterol-fed rabbits at all concentrations of acetylcholine tested. There was no difference
between responses in preparations from control and
cholesterol plus vitamin E-fed rabbits. Relaxant responses to the calcium ionophore A23187 were significantly greater in preparations from cholesterol plus
vitamin E-fed rabbits compared with cholesterol-fed
rabbits at 3.0, 10, and 30 /xmol/L (Fig 2). Preparations
from control versus cholesterol-fed rabbits and also
from control versus cholesterol plus vitamin E-fed
rabbits did not vary in their response to A23187.
Relaxant responses to sodium nitroprusside measured
in preparations from the three groups were not different
over the concentration range tested (Fig 3).
Both noradrenaline (0.01 to 300 /imol/L) and serotonin (0.01 to 30 /xmol/L) produced a dose-dependent
contractile response in all carotid artery preparations
tested at resting tone. There was no significant difference between responses to noradrenaline and those to
serotonin in artery segments obtained from rabbits fed
any of the three dietary regimens (Figs 4 and 5).
Copper Oxidation of 0VLDL
The copper-induced oxidation of /3VLDL from rabbits fed the cholesterol plus vitamin E diet was inhibited
compared with the ability of £SVLDL isolated from the
plasma of rabbits fed a cholesterol-enriched diet alone
(Fig 6).
Histology
Silver nitrate stained the endothelial cell membrane
and confirmed the presence of a normal intimal endothelial monolayer (Fig 7). Oil red O staining revealed no
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4
FIG 1. Graph of isolated transverse ring preparations of the
rabbit carotid artery with tone raised by noradrenaline (10
/imol/L). Cumulative concentration-response curves to acetylcholine (ACh) (0.1 to 100 /imol/L) in preparations taken from
rabbits fed control (•, n=8), 1% cholesterol (A, n=10), and 1%
cholesterol plus 0.2% vitamin E (a, n=8) diets for 4 weeks. Data
points are means, with SEM shown by vertical bars. Statistical
analysis between the three groups was carried out by the
Bonferroni method, in which analysis of variance indicated a
significant difference between groups. + P<.05, *P<.01 compared with control group. t t P < . 0 1 , t t t P < 0 0 1 compared with
cholesterol group.
Stewart-Lee et al
100
+
T____
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T
T ^^—•
'
Vitamin E in Hypercholesterolemia
497
T I
80
% Relaxatlo
c
eo
40
/
;
1
20
n
o.oo
6.5
5.5
- log A23187 cone (M)
6
4.5
- log NA cone. (M)
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FIG 2 Graph oi isolated transverse ring preparations of the
rabbit carotid artery with tone raised by noradrenaline (10
Mmol/L). Cumulative concentration-response curves to the calcium ionophore A23187 (0.1 to 30 /imol/L) in preparations taken
from rabbits fed control (•, n=8), 1% cholesterol (A, n = 10), and
1% cholesterol plus 0.2% vitamin E (a, n=8) diets for 4 weeks.
Data points are means, with SEM shown by vertical bars.
Statistical analysis between the three groups was carried out by
the Bonferroni method, in which analysis of variance indicated a
significant difference between the groups. *Signrficant difference, P<.05 compared with the cholesterol-fed group.
or minimal (<5%) intimal lipid deposition in vessels
from both cholesterol only- and cholesterol plus vitamin
E-fed animals. Vessel segments from animals on the
control diet also showed no oil red O staining. Light and
electron microscopy revealed that the appearance of the
carotid arteries from the cholesterol-fed animals was
essentially normal. At this time, the endothelium was
intact, and no subendothelial foam cells could be detected. Occasional adherent leukocytes were observed
by scanning electron microscopy in cholesterol-fed and
cholesterol plus vitamin E-treated animals.
100
Fra 4. Graph of isolated transverse ring preparations of the
rabbit carotid artery at resting tone. Cumulative concentrationresponse curves to noradrenaline (NA) (0.01 to 300 ^mol/L) in
preparations taken from rabbits fed control (•, n=8), 1% cholesterol (A, n=10), and 1% cholesterol plus 0.2% vitamin E (•, n=8)
diets for 4 weeks. Data points are means, with SEM shown by
vertical bars.
Discussion
Hypercholesterolemia Impairs Endothelial Cell
Signal Transduction
Several studies have shown that hypercholesterolemia
inducesmacrovascularendothelial dysfunction.2224Our
data confirm that receptor-mediated, endothelium-dependent responses are rapidly impaired in the carotid
artery of the cholesterol-fed rabbit and precede the
development of overt atherosclerotic lesions.
Endothelium-dependent vasodilatation is mediated
by EDRF, which has been identified as nitric oxide or a
closely related molecule. There are a number of possible sites at which hypercholesterolemia may interfere
with receptor-mediated responses. In a recent review,
Flavahan25 presented the evidence supporting the view
that hypercholesterolemia affects a G protein-depen3.00
2 50
2.00
°
60
1.50
1.00
0.50
0.00
6
5.5
5
4.5
- log SNP cone. (M)
3.5
Fra 3. Graph of isolated transverse ring preparations of the
rabbit carotid artery with tone raised by noradrenaline (10
/tmol/L). Cumulative concentration-response curves to sodium
nitroprusside (SNP) (0.1 to 300 ^molA.) in preparations taken
from rabbits fed control (•, n=8), 1% cholesterol (A, n=10), and
1% cholesterol plus 0.2% vitamin E (•, n=8) diets for 4 weeks.
Data points are means, with SEM shown by vertical bars.
7.5
7
6.5
6
5.5
- log serotonin cone. (M)
4.5
FIG 5. Graph of isolated transverse ring preparations of the
rabbit carotid artery at resting tone. Cumulative concentrationresponse curves to serotonin (0.01 to 30 jimol/L) in preparations
taken from rabbits fed control (•, n=8), 1% cholesterol (A,
n=10), and 1 % cholesterol plus 0.2% vitamin E (•, n=8) diets for
4 weeks. Data points are means, with SEM shown by vertical
bars.
498
Arteriosclerosis and Thrombosis
Vol 14, No 3 March 1994
0.5
1.0
2.0
TIME (hours)
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FIG 6. Graph of copper-induced oxidation of pooled /3-very-lowdensity lipoprotein isolated from cholesterol- (•) and cholesterol
plus vitamin E-fed rabbits (•) at incubation times of 15 and 30
minutes and 1 , 2 , 4 , and 6 hours. TBARS were determined as
described in the "Methods" section and are expressed as
malondialdehyde (MDA) equivalents. TBARS indicates thiobarbituric acid-reactive substances.
dent pathway. Other authors have proposed effects on
the availability of the EDRF precursor L-arginine,26 the
stability of nitric oxide,5 or the activity of smooth muscle
cell guanylate cyclase.27
We found that although hypercholesterolemia caused
impaired responses to acetylcholine, responses to the
calcium ionophore A23187 and sodium nitroprusside
were unaffected. This suggests that at this time point,
hypercholesterolemia has led to a defect in the muscarinic receptor/G protein-coupling mechanism proximal
to the level of intracellular calcium release.
Vitamin E Protects Endothelium From
Cholesterol-Induced Injury
The generation of ROS is enhanced in atherosclerotic
arteries. 78 These free radical species can inactivate
EDRF 910 or lead to oxidative modification of lipoproteins such as LDL and /3VLDL.28 31 Some of the byproducts of lipoprotein oxidation, including hydroperoxides, reactive aldehydes, and lysophosphatidyl
choline, also have direct cytotoxic effects.
Vitamin E is a potent chain-breaking antioxidant that
inhibits lipoprotein oxidation and scavenges ROS. We
found that dietary supplements of vitamin E preserved
the vasodilator responses to acetylcholine in cholesterol-fed rabbits. In these animals, the responses to
A23187 were also significantly enhanced above control
values, although the responses to sodium nitroprusside
were unaltered. These data suggest that vitamin E may
enhance EDRF generation or preserve its bioactivity,
perhaps by preventing its destruction by ROS such as
superoxides. In addition, vitamin E would inhibit the in
vivo oxidation of /3VLDL (since the in vitro oxidation of
/3VLDL from vitamin E-fed, hypercholesterolemic rabbits was inhibited), thus preventing an inhibition of
endothelium-mediated responses resulting from the
presence of oxidized /3VLDL.
In support of our findings, Miigge et al32 have shown
that treatment of atherosclerotic rabbits with polyethylene glycolated superoxide dismutase for 1 week resulted
in enhanced responses to acetylcholine and A23187 but
not sodium nitroprusside. Since this enhancement was
not observed in control rabbits, it was concluded that
the endothelial dysfunction was likely to have been
caused at least in part by the increased generation of
ROS. There have been several other treatments in
animals fed a cholesterol-rich diet that have been shown
to improve endothelium-dependent relaxations. These
include the calcium antagonist PN200110 and dipyridamole.33-34 In both cases, however, treatment also led
to a reduction in the formation of arterial lesions, which
would have contributed to the improvement of functional responsiveness of the endothelium.
In conclusion, this study suggests that dietary vitamin
E has a protective role on the endothelium signaling
FIG 7. Histological section of endothelium from a cholesterol-fed rabbit stained
with 0.25% silver nitrate showing an intact vascular endothelium. Original magnification x400.
Stewart-Lee et al Vitamin E in Hypercholesterolemia
lisms, which are compromised after cholesterol
. Vitamin E appears to exert its protective effects
sites in the signal transduction pathway, one
il to the release of intracellular calcium, the
t the level of EDRF generation or bioactivity.
Acknowledgments
/ork was supported by a grant from Ono Pharmaceui, Ltd, Osaka, Japan. The authors wish to thank Dr Shu
or assistance in measuring serum cholesterol levels.
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28. Jacobs M, Plane F, Bruckdorfer KR. Native and oxidised lowdensity lipoproteins have different inhibitory effects on endothelium-derived relaxing factor in the rabbit aorta. Br J Pharmacol.
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Transition to SI Units
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At its October 1990 meeting the Scientific Publishing
Committee explored the use and prevalence of Systeme
International (SI) units for reporting measures of clinical and laboratory data. The committee since has
sanctioned the use of SI units in the American Heart
Association (AHA) journals.
The SI, an update of the metric system, is the
outcome of a century of effort to provide a common
system of measurement between nations and among the
sciences. To promote its use, which can reduce the
present confusion about measurements, the World
Health Assembly in 1977 recommended the use of SI
units in medicine.
The 5/ base units are the meter, kilogram, second,
ampere, kelvin, candela, and mole, respectively representing length, mass, time, electric current, temperature, luminous intensity, and amount of substance. By
multiplying a base unit by itself, or by combining two or
more basic units by multiplication or division, many
units can be formed, known as Si-derived units. Examples of derived units are the square meter, cubic meter,
mole per cubic meter, pascal (Pa), and joule (J).
Exceptions to the rule for SI unit conversion as
currently applied to biomedical sciences include blood
pressure, oxygen pressure, and enzyme activity. Retained as presently used are temperature, the pH scale,
and the use of liter for volume. Table 1 illustrates the
measurements excluded from SI unit conversion.
In the AHA journals, an average article contains few
items that need conversion. Often the same conversion
is made over and over in a manuscript and takes little
extra effort. It is our belief that, in return for a small
effort, the AHA can take a large step, along with many
other international and domestic journals, toward perpetuating a common system for reporting medical and
scientific measurements. The SI unit is to be used in
text, followed by the presently used measurement in
parentheses.
The accompanying conversion table (Table 2) lists the
measurements most commonly used in the AHA jourTABLE 1.
Current Unit
mm Hg
Oxygen pressure
mm Hg
H
concentration
Volume
Conversion
Factor
SI Unit
M (molar)
1
mol/L
mM
1
mmol/L
torr
1
mm Hg
atm
101.325
kPa
0.01
No units
36-54
0.36-0.54
1
1012/L
4.0-6.0
4.0-6.0
0.001
109/L
5000-10 000
5.0-10.0
0.02586
mmol/L
<200
<5.20
1
mmol/L
135-145
135-145
1
mmol/L
3.5-5.0
3.5-5.0
0.5
mmol/L
4.5-5.5
2.25-2.75
4.2
J
1
S
Current Unit
Current
SI
Concentration
Pressure
Hematocrit
%
Red blood
cell count
106/mm3
White blood
cell count
/mm3
Cholesterol
mg/dL
Sodium ion
(Na+)
mEq/L
Potassium ion
<K+)
mEq/L
Calcium ion
(Ca2+)
Calories
Measurement
Temperature
Normal Laboratory
Valuest
Energy
Blood pressure
+
TABLE 2. Examples of Measurement Conversions to
Systeme International (SI) Units for American Heart
Association Journals*
mEq/L
Measurements Currently Not Converted
to Systeme International (SI) Units in
Biomedical Applications
Enzyme activity
nals and their corresponding SI units. A review of this
table may serve as an introduction to the forthcoming
transition to SI units.
IU
pH
°C
L
Conductance
mho
*For a brief discussion of the development and use of SI units,
see World Health Organization: The SI for the Health Professions,
Geneva, Switzerland: World Health Organization, 1982. For a
convenient list of commonly used laboratory measurement conversions to SI units, see "SI unit implementation-the next step"
(editorial) in JAMA (1988;260:73-76).
tFor illustration only; normal values may vary by laboratory.
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Vitamin E protects against impairment of endothelium-mediated relaxations in
cholesterol-fed rabbits.
A L Stewart-Lee, L A Forster, J Nourooz-Zadeh, G A Ferns and E E Anggård
Arterioscler Thromb Vasc Biol. 1994;14:494-499
doi: 10.1161/01.ATV.14.3.494
Arteriosclerosis, Thrombosis, and Vascular Biology is published by the American Heart Association, 7272 Greenville
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Copyright © 1994 American Heart Association, Inc. All rights reserved.
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