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Antihypertensive Effects of Onion on NO


Synthase Inhibitor-induced Hypertensive Rats and
Spontaneously Hypertensive Rats
a

Yoko SAKAI , Tetsuo MURAKAMI & Yukiko YAMAMOTO


a

Graduate School of Human Life Science, Osaka City UniversitySugimoto 3-3-138,


Sumiyoshi-ku, Osaka 558-8585, Japan
b

Faculty of Agriculture, Kinki UniversityNakamachi 3327-204, Nara 631-8505, Japan


Published online: 22 May 2014.

To cite this article: Yoko SAKAI, Tetsuo MURAKAMI & Yukiko YAMAMOTO (2003) Antihypertensive Effects of Onion on
NO Synthase Inhibitor-induced Hypertensive Rats and Spontaneously Hypertensive Rats, Bioscience, Biotechnology, and
Biochemistry, 67:6, 1305-1311, DOI: 10.1271/bbb.67.1305
To link to this article: http://dx.doi.org/10.1271/bbb.67.1305

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Biosci. Biotechnol. Biochem., 67 (6), 13051311, 2003

Antihypertensive Eects of Onion on NO Synthase Inhibitor-induced


Hypertensive Rats and Spontaneously Hypertensive Rats
Yoko SAKAI,1 Tetsuo MURAKAMI,2 and Yukiko YAMAMOTO 1,
1Graduate

School of Human Life Science, Osaka City University, Sugimoto 3-3-138, Sumiyoshi-ku,
Osaka 558-8585, Japan
2Faculty of Agriculture, Kinki University, Nakamachi 3327-204, Nara 631-8505, Japan

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Received December 19, 2002; Accepted February 26, 2003

This study was designed to show the eects of onion


on blood pressure in NG-nitro-L-arginine methyl ester
(L-NAME) induced-hypertensive rats and stroke prone
spontaneously hypertensive rats (SHRSP) using dried
onion at 5% in their diets. For the experiment with LNAME induced-hypertensive rats, male 6-weeks-old
Sprague-Dawley rats were given tap water containing Lkg BW W
day. In this experiNAME to deliver 50 mg W
ment, we found distinct antihypertensive eects of
onion on the L-NAME induced-hypertensive rats and
the SHRSP. Dietary onion decreased the thiobarbituric
acid reactive substances (TBARS) in plasma in these
hypertensive rats. Also, onion increased the nitrate W
nitrite (products of nitric oxide (NO)) excreted in urine
and the NO synthase (NOS) activity in the kidneys in
SHRSP. These results suggested that the increased NO
caused by the greater NOS activity, and additionally by
the increased saving of NO by the antioxidative activity
of onion, was one of the cause of the antihypertensive
eect of onion in SHRSP. In the L-NAME induced
hypertensive rats, onion did not signicantly block the
inhibition of NOS activity by L-NAME, and decreased
nitrite excretion in urine was not restored. The
nitrate W
mechanism of the antihypertensive eect of onion probably involves increased saving of NO by antioxidative
activity of onion in L-NAME induced-hypertensive rats.
Key words:

hypertension; onion; NO synthase inhibitor; SHRSP; antioxidant

Onion ( Allium cepa) and garlic ( Allium sativum)


are said to have a benecial medicinal eect on various aspects including blood platelet aggregation and
cholesterol and glucose levels in serum.16) For the
eects of blood pressure, the antihypertensive eects
of garlic on the hypertensive patient,7,8) spontaneously hypertensive rats (SHR),9) and nitric oxide
synthase (NOS) inhibitor-induced hypertensive rats 10)
have been studied. The eects of onion on blood
pressure have been studied less extensively, the only
study we found being a report of Louria et al. who

administered crude onion extract to hypertensive


patients.11) Kiviranta et al. failed to show the antihypertensive eects of an ethanolic extract of onion
on SHR.12)
Recent studies show the antihypertensive eects of
antioxidative components in food including atocopherol 13,14) and ascorbic acid.1417) Onion is a
good source of quercetin, which is one of the most
abundant avonol-type avonoids in fruits and
vegetables.18) Quercetin is present in onion in glycoside forms, and most of it is in a highly absorbable
glucoside form.19) Fr emont et al. showed that dietary
avonoids (quercetincatechin, 2:1) reduced lipid
peroxidation in rats fed polyunsaturated fat diet.20)
Onion also contains many kinds of sulfur compounds. These are alkyl cysteine sulfoxides such
as S-propenylcysteine sulfoxide, S-propylcysteine
sulfoxide, and S-methylcysteine sulfoxide.21,22)
Sulfoxides have been shown to be strongly antioxidative.2325)
Nitric oxide (NO) is produced from arginine by
NOS, and is responsible for acetylcholine-mediated
vascular relaxation. The blockade of NO synthesis by
the injection of NOS inhibitors, such as N G-nitro-Larginine methyl ester (L-NAME), causes hypertension.26,27) Reduced NOS activity or decreased NO
concentration might lead to an elevated blood
pressure.
In this study the eects of onion on the blood
pressure in the L-NAME induced-hypertensive rats
and the stroke-prone spontaneously hypertensive rats
(SHRSP) were studied. The eects of onion on the
NO metabolism were also studied.

Materials and Methods


Animals and experimental diets. For the experiment with L-NAME induced-hypertensive rats, male
6-weeks-old Sprague-Dawley rats weighing approximately 200 g were obtained from Clea Japan, Inc.
(Osaka, Japan). For 4 or 5 days the animals were

To whom correspondence should be addressed. Fax: 81-6-6605-2819; E-mail: Yamamotolife.osaka-cu.ac.jp

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1306

Y. SAKAI et al.

given free access to water and a basal diet. They were


randomly divided into three test groups of six
animals each to average the initial body weight and
systolic blood pressure. One group received a control
diet and, for drinking, tap water (Control group).
The other two groups were fed a control diet (LN
group) or an onion diet (LN-ON group), and were
given tap water containing L-NAME to deliver 50 mg
kg BW W
day. The concentration of L-NAME in tap
W
water was adjusted on a daily basis to ensure proper
dosing. For the experiment with SHRSP, male and
female SHRSP were obtained from the colonies established in Kinki University (Nara, Japan) and were
bred in our laboratory. Male 15 week old SHRSP
were randomly divided into 2 groups (n6) to
average the initial body weight and systolic blood
pressure, and were fed a control diet (Control group)
or an onion diet (ON group) with tap water to drink.
For experiments with L-NAME induced hypertensive rats and with SHRSP, the animals were housed
individually in cages with wire mesh bottoms in a
room kept at 2219C and with a dark period from
20:00 to 8:00 h. Food and water were given ad libitum for the 4-week duration of the experiment. The
composition of a basal diet was as follows (wtz):
corn oil, 5.0; mineral mixture, 3.5; vitamin mixture,
1.0; choline bitartrate, 0.1; casein, 20.0; and corn astarch to make 100. The compositions of the control
diet and the onion diet were the same as the basal diet
except that 5z of the corn a-starch was replaced with
cellulose and onion powder, respectively. For the
preparation of onion powder, onion harvested on
June 2000 in Izumisano was used. The onions were
crushed, heated to 80909C by a microwave heater
to cause denaturation of enzyme activity, and freezedried. The composition of the mineral mixture is
AIN-93G-MX and that of vitamin mixture is AIN93-VX.28)
After the 4-week growing period, the rats were
starved overnight, anesthetized with ether, and their
blood was collected in a heparinized syringe from the
abdominal aorta. The plasma was separated by
centrifugation at 10,000g at 49C for 15 min, and
stored at 809C while awaiting biochemical analysis. Immediately after blood sampling, the abdominal aorta and kidneys were harvested, cleaned, blotted, and stored at 809C until they were processed.
All experiments were done under the Guideline for
Animal Experiment in Osaka City University and the
Notication No. 6 of the Japanese government.

Blood pressure. The systolic blood pressure was


measured at the end of every week using the tail-cu
method 29) with an instrument (BP98, Softron Inc.
Japan). The tails of rats were heated in an oven and
the average of three readings was taken as the nal
value.

TBARS measurement. Lipid peroxides in blood


plasma were measured as the thiobarbituric acid
reactive substances (TBARS) by the spectrometry
method 30) and were expressed as the amount of MDA
in plasma.
NOS activity. NOS activity was measured by the
method of Bredt and Snyder.31) A kidney and the abdominal aorta were homogenized with ve volumes
of 50 mM HEPES (pH 7.4) containing 1 mM
dithiothreitol, 1 mM EDTA, 5 mg W
ml phenylmethylsulphonyl uoride, 5 mg W
ml of pepstatin, and 5 mg W
ml of aprotinine. The homogenate was centrifuged
for 5 min at 11,000g, and the supernatant was used
for the NOS assays. Assay mixture consisted of
12.5 mM HEPES (pH 7.3), 1.2 mM MgCl2, 0.96 mM
CaCl2, 3 mM tetrahydrobiopterin, 1 mM FAD, 1 mM
FMN, 0.024 mM L-arginine, 0.01 mmol L-[U-14C]arginine (1.5 kBq), 0.12 mM NADPH, and 0.02 ml of
homogenate supernatant in a nal volume of 0.1 ml.
Activity was expressed as the amount of citrulline
produced per protein. Protein was measured by the
method of Lowry et al.32)
Nitric oxide in urine. Urine was collected at the last
3 days of the growing period by placing the rats in
metabolic cages. The total nitrate and nitrite concentration in urine was measured by reacting with Greiss
reagent following the procedure described by Wu et
al.33) Results were expressed as total nitrate and
nitrite per creatinine in urine.
Statistical analysis. The data was expressed as
meanSEM for six rats. Data were analyzed by the
analysis of variance (one way ANOVA) and multiple
range comparisons by Fisher's protected least signicant dierence (PLSD) procedure or an unpaired
Student's t-test using StatView, Abacus Concepts,
Inc., Berkeley, CA. A P value of 0.05 was considered signicantly dierent.

Results
Eects of onion on L-NAME induced-hypertensive
rats
As Table 1 shows, average body weight gain and
food intake for 4 weeks in the Control, LN, and LNON groups were not dierent from each other.
The NOS activity in kidney and aorta was signicantly lower in rats of LN and LN-ON groups
than that in rats of the Control group, although the
activity in the aorta in the LN-ON group was not
signicantly dierent from that in the Control group
(Table 1).
The average systolic blood pressure of three groups
at the start of experiment was about 135 mmHg
(Fig. 1). The blood pressure was increased gradually
in rats of the LN group, and rose to about 180 mmHg

Antihypertensive Eects of Onion


Table 1.

1307

Eects of Dietary Onion on Growth, Food Intake, and NOS Activity in Rats Administered L-NAME

day)
Body weight gain (g W
day)
Food intake (g W
NOS activity
min W
mg protein)
Kidney (pmol W
Aorta (pmol W
min W
mg protein)

Control

LN

LN-ON

6.630.47
20.50.6

6.300.39
19.30.6

6.420.23
18.90.7

0.3120.061a
0.1220.01a

0.1760.019b
0.0820.007b

0.2000.019b
0.0940.011ab

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MeanSEM (n6).
Values within the same row with dierent superscripts are signicantly dierent from each other ( p0.05).

Fig. 1. Eects of Dietary Onion on Systolic Blood Pressure in LNAME Induced Hypertensive Rats.
, Control group; , LN group; , LN-ON group. Values
with dierent superscript letters at a same time are signicantly
dierent from each other ( p0.05).

at the end of the 4-week growing period. The blood


pressure in rats of the LN-ON group increased more
slowly and grew to about 160 mmHg at the end of
4 weeks. The signicant antihypertensive eect of
onion was observed from 1 to 4 weeks.
The TBARS in plasma was signicantly higher in
rats of the LN group than the Control group (Fig. 2).
The value was decreased to the level of the Control
group by feeding the onion diet to the LN-ON group.
The NO excreted in urine was signicantly lower in
rats of the LN group compared to the Control group
(Fig. 3). In the LN-ON group, NO in urine was not
signicantly dierent from that in the Control group.

Eects of onion on SHRSP


As Table 2 shows, the growth and food intake in
SHRSP of the ON group for the 4-week's duration of
the experiment were not dierent from those of
Control group.

Fig. 2. Eects of Dietary Onion on the TBARS in Plasma in LNAME Induced Hypertensive Rats.
Values with dierent superscript letters are signicantly dierent from each other ( p0.05).

Average systolic blood pressure of the two groups


at the start of experiment was about 200 mmHg. The
blood pressure increased gradually in the Control
group, and rose to about 235 mmHg at the end of the
growing period (Fig. 4). The blood pressure of the
ON group increased much more slowly, attaining
about 215 mmHg after 4 weeks, and the signicant
antihypertensive eect of onion was observed from 1
to 4 weeks.
The TBARS in plasma was signicantly lower in
the ON group than that of the Control group (Fig. 5).
The NOS activity in kidney and aorta was higher in
the ON group than that of the Control group,
although the dierence was not signicant for the
aorta (Fig. 6).
The NO excreted in urine was signicantly higher
in the ON group than the Control group (Fig. 7).

Discussion
The eects of onion on blood pressure have not
been well established in previous literature. Kiviranta

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1308

Y. SAKAI et al.

Fig. 3. Eects of Dietary Onion on the NO Excretion in Urine in


L-NAME Induced Hypertensive Rats.
The NO excreted in urine was expressed as total nitrate and
nitrite per creatinine in urine. Values with dierent superscript
letters are signicantly dierent from each other ( p0.05).

Table 2.
SHRSP

Eects of Dietary Onion on Growth and Food Intake in

day)
Body weight gain (g W
Final body weight (g)
day)
Food intake (g W

Control

ON

1.080.17
2805
15.00.2

0.910.07
27710
14.40.2

Fig. 4. Eects of Dietary Onion on Systolic Blood Pressure in


SHRSP.
, Control group; , ON group. *p0.05 vs. Control group
at the same time.

MeanSEM (n6).

et al. failed to show any antihypertensive eects of


an ethanolic extract of onion on SHR by the oral
administration for up to 7 weeks. 12) In this experiment, we showed distinct antihypertensive eects of
onion on L-NAME induced-hypertensive rats and
SHRSP by using 5z dried onion in the diets. The
reason of the dierence of this result with the result
of Kiviranta et al. is not clear. The possible dierence
in the chemical composition and dose levels between
an etanolic extract of onion and whole onion may be
the reason for the dierent results for antihypertensive eect.
Several recent studies have provided compelling
evidence for the generation of increased levels of
reactive oxygen species (ROS) in the vascular tissues
of SHR.3436) The role of oxidative stress on the genesis and maintenance of hypertension has been supported by amelioration of hypertension in SHR by
the administration of many kinds of antioxidants.1317) In this experiment, onion was antioxidative for both L-NAME induced-hypertensive rats and
SHRSP, suggesting that the antioxidative compo-

Fig. 5. Eects of Dietary Onion on the TBARS in Plasma in


SHRSP.
*p0.05 vs. Control group.

nents in onion are responsible for the antihypertensive activity.


There are many components in onion known as
potent antioxidants, and one of them is quercetin.
The antioxidative activity of quercetin has been
shown in rats fed a polyunsaturated fat diet.20)
Manach et al. detected an antioxidative activity of
quercetin recovered from human plasma.37) Onion

Antihypertensive Eects of Onion

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Fig. 6. Eects of Dietary Onion on the NOS Activity in Kidney


and Aorta in the SHRSP.
*p0.05 vs. Control group.

1309

generation and maintenance of hypertension in SHR


by several mechanisms, including inactivation of
endothelium-derived NO. ROS have been shown to
react quickly with NO, and its consequent inactivation of NO is responsible for the blockade of acetylcholine-mediated vascular relaxation.4042)
ROS may also contribute to the depletion of the
NOS cofactor tetrahydrobiopterin. Recently, it has
been reported that the absence of tetrahydrobiopterin leads to an uncoupling of the L-arginine-NO pathway and then causes superoxide formation instead
of NO formation.43) Supplementation with tetrahydrobiopterin suppressed the development of
hypertension in SHR.44) These results suggest that
antioxidants might protect the depletion of tetrahydrobiopterin and then increase NOS activity.
The possible eects of onion components other
than quercetin and sulfur compounds on the antihypertensive activity of onion are considerable.
Ingested nitrate W
nitrite from onion in the diet may be
eective physiologically, and may play a part in the
increase in urinary nitrate W
nitrite. Also, arginine
from onion in the diet may increase NO. Much
research has shown that intravenous or oral administration of arginine increases NO synthesis in animal
and human experiments.45,46) Additional studies must
be done to understand the roles of these components
on antihypertensive activity of onion.

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Fig. 7. Eects of Dietary Onion on the NO Excretion in Urine in
SHRSP.
*p0.05 vs. Control group.

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