Original Article
The antioxidant effects of green tea reduces blood
pressure and sympathoexcitation in an experimental
model of hypertension
Michelle L. Garcia a, Roberto B. Pontes a, Erika E. Nishi a, Flavia K. Ibuki b, Vanessa Oliveira c,
Alexandra C.H. Sawaya d, Patrcia O. Carvalho e, Fernando N. Nogueira b, Maria do Carmo Franco c,
Ruy R. Campos a, Lila M. Oyama a, and Cassia T. Bergamaschi a
Background: Oxidative stress is a key mediator in the
maintenance of sympathoexcitation and hypertension in
human and experimental models. Green tea is widely
known to be potent antioxidant.
Objective: We aimed to evaluate the effects of green tea
in a model of hypertension.
Methods: Hypertension was induced by the nitric
oxide synthase inhibitor [N-nitro-L-arginine-methyl-ester
(L-NAME); 20 mg/kg per day, orally, for 2 weeks] in male
Wistar rats. After the first week of L-NAME treatment,
animals received green tea ad libitum for 1 week. At
the end of the treatment period, blood pressure, heart
rate, baroreflex sensitivity, renal sympathetic nerve
activity, and vascular and systemic oxidative stress were
assessed.
Results: L-NAME-treated animals exhibited an increase in
blood pressure (165  2 mmHg) compared with control rats
(103  1 mmHg) and green tea treatment reduced
hypertension (119  1 mmHg). Hypertensive animals
showed a higher renal sympathetic nerve activity (161  12
spikes/s) than the control group (97  2 spikes/s), and
green tea also decreased this parameter in the
hypertensive treated group (125  5 spikes/s). Arterial
baroreceptor function and vascular and systemic oxidative
stress were improved in hypertensive rats after green tea
treatment.
Conclusions: Taken together, short-term green tea
treatment improved cardiovascular function in a
hypertension model characterized by sympathoexcitation,
which may be because of its antioxidant properties.
Keywords: green tea, hypertension, oxidative stress
Abbreviations: BP, blood pressure; CAT, catalase; DAF-2,
4,5-diamino fluorescein diacetate; DHE, dihydroethidium;
EGCG, epigallocatechin-3-gallate; eNOS, endothelial nitric
oxide synthase; GPx, glutathione peroxidase; HR, heart
rate; L-NAME, N-nitro-L-arginine-methyl-ester; MAP, mean
arterial pressure; MDA, malondialdehyde; NO, nitric oxide;
ROS, reactive oxygen species; rSNA, renal sympathetic
nerve activity; SEM, standard error of the mean; SOD,
superoxide dismutase
348 www.jhypertension.com
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INTRODUCTION
I
t is well known that activation of the sympathetic
nervous system plays an important role in the patho-
genesis of hypertension in humans and in experimen-
tal models [1]. Previous studies have shown that a reduction
in renal sympathetic nerve activity (rSNA) is associated
with a reduction in blood pressure (BP) in experimental
hypertension [1,2]. Furthermore, ongoing clinical trials have
also shown that renal nerve ablation produces a long-term
reduction in BP in resistant hypertensive patients, [3] cor-
roborating that excessive activity in rSNA contributes to
hypertension. Additionally, hypertension is also associated
with endothelial dysfunction [4,5].
Several studies have shown that increased oxidative
stress is a key mediator in the maintenance of sympathoex-
citation and hypertension [1,4]. In experimental models of
hypertension, scavenging of reactive oxygen species (ROS)
systemically and in the central nervous system significantly
reduced BP and endothelial dysfunction [1]. Such evidence
suggests that antioxidants are a promising additional treat-
ment for hypertension.
Epidemiological data have demonstrated that green
tea consumption is beneficial in cardiovascular diseases,
possible because of its antioxidant effect and its important
biological properties [6]. One possible beneficial effect of
green tea is related to the presence of polyphenols, known
as flavanoids. Catechins are flavanoids, and epigallocate-
chin-3-gallate (EGCG) is the primary catechin components
of green tea. EGCG is considered to be the component
Journal of Hypertension 2017, 35:348354
a
Department of Physiology, Escola Paulista de Medicina, Universidade Federal de Sao
Paulo, bDepartment of Biomaterials and Oral Biology, Faculdade de Odontologia,
Universidade de Sao Paulo, cDepartment of Medicine, Universidade Federal de Sao
Paulo, Sao Paulo, dDepartment of Plant Biology, Universidade Estadual de Campinas,
Campina and eLaboratory of Multidisciplinary Research, Universidade Sao Francisco,
Sao Paulo, Brazil
Correspondence to Cassia T. Bergamaschi, PhD, Disciplina de Fisiologia Cardiovas-
cular, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Rua Botucatu,
862, CEP 04023-060, Sao Paulo, SP, Brazil. Tel: +55 11 5573 7820 ext. 24;
fax: +55 11 5573 7820; ext. 5; e-mail: bergamaschi.cassia@unifesp.br
Received 2 June 2016 Revised 8 August 2016 Accepted 16 September 2016
J Hypertens 35:348354 Copyright 2017 Wolters Kluwer Health, Inc. All rights
reserved.
DOI:10.1097/HJH.0000000000001149
Volume 35  Number 2  February 2017

with the highest biological properties responsible for green
teas major antioxidant effects [7].
Previous studies demonstrated that chronic green tea or
green tea component treatment led to a reduction in BP,
and these effects were mainly correlated with a reduction in
oxidative stress [8,9]. It was also suggested that catechins
present in green tea were able to improve vascular function
[10,11]. However, the underlying mechanisms by which
green tea reduces BP are still unclear. Our hypothesis is that
green tea influences sympathoexcitation, especially in
regards to sympathetic vasomotor activity to the kidneys,
key organs in the control of BP. Therefore, the aim of the
present study was to verify the effects of green tea con-
sumption on BP levels, baroreflex control of heart rate (HR)
and baseline rSNA in an experimental model of hyperten-
sion induced by nitric oxide synthesis inhibition. Moreover,
we also evaluated the role of green tea consumption on the
systemic antioxidant system and the local effect on resist-
ance blood vessels.
METHODS
All experimental procedures used in this study were con-
ducted under guidelines recommended by the National
Institutes of Health and approved by the Ethics in Research
Committee from the Universidade Federal de Sao Paulo-
Escola Paulista de Medicina (process No.0381/12). Male
Wistar rats (250300 g) were housed in group cages, given
access to rat chow and water ad libitum, and maintained in
a temperature-controlled environment (238C) with a 12-h
light/dark cycle. Animals were supplied by the animal care
facility of our institution (Centro de Desenvolvimento de
Modelos Experimentais).
Experimental protocol
The rats were divided into four groups: CT: control rats
received only vehicle (water); CT GT control rats treated
with green tea; H: hypertensive rats treated with vehicle and
HGT: hypertensive rats treated with green tea. The study
was divided into two independent series of experiments. In
the first series, mean arterial pressure (MAP), heart rate, the
arterial baroreceptor reflex control of HR were assessed. In
a second series of experiments, blood samples and mes-
enteric arteries were collected for analysis.
Induction of hypertension
Hypertensive animals were obtained using N-nitro-L-
arginine-methyl-ester (L-NAME, Sigma-Aldrich, St.Louis,
Missouri, USA), an inhibitor of nitric oxide synthase.
Animals were treated orally by gavage with L-NAME
(20 mg/kg per day) for 2 weeks.
Green tea treatment
Green tea (Leao Junior, Curitiba, Parana, Brazil) was admin-
istered ad libitum in substitution of water for 1 week. Green
tea treatment started 1 week after the beginning of treat-
ment with L-NAME or vehicle and lasted for 1 week. The
green tea was prepared daily by infusing three tea bags
(9.6 g) in boiling tap water (1.0 litre) for 5 min, following the
manufacturers recommendation. Each animal drank
approximately 18 ml/day. We used a dose 12 mg/kg per
Journal of Hypertension
Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved.
Green tea decreases sympathoexcitation
day of EGCG that was previously reported to be effective
in reducing BP in clinical studies [12].
To determine the amount of vehicle or green tea intake
and the urinary volume after treatment, animals were
housed for 48 h in metabolic cages (Nalgene, Ugo Basile,
Varese, Italy). The first 24 h were considered an adaptation
period.
Cardiovascular parameters and cardiac arterial
baroreceptor reflex function in conscious rats
Rats under ketamine and xylazine anesthesia had the fem-
oral vein and artery catheterized for the i.v. injection of
drugs and the direct recording of arterial pressure, respect-
ively. After surgical recovery (24 h), basal values of MAP
and HR were recorded in conscious rats for at least 15 min.
Bolus intravenous injections were made with increasing
doses of phenylephrine (3510 mg/kg i.v., Sigma-Aldrich)
and sodium nitroprusside (51520 mg/kg, i.v., Sigma-
Aldrich) to induce BP increases or decreases and reflex
bradycardia or tachycardia, respectively. Values of match-
ing MAP variations (DMAP) with reflex HR (DHR) responses
were separately plotted for each vasoactive drug to create
linear regression curves of baroreceptor function for each
group. Their slopes (bpm/mmHg) were compared with test
changes in baroreflex sensitivity among groups.
Renal sympathetic nerve activity
After recording the cardiovascular parameters in conscious
rats, the same animals were slowly anesthetized with ure-
thane (1.2 g/kg, i.v., Sigma-Aldrich). The left renal nerve was
retroperitoneally exposed, placed on bipolar silver electro-
des, and covered with paraffin oil. The signal from the renal
nerve was displayed on an oscilloscope (Tektronix digital
series) 220 (Tektronix, Beaverton, Oregon, USA). The nerve
activity was amplified (gain 20K, Neurolog, Digitimer, Hert-
fordshire, UK), filtered by a bandpass filter (1001000 Hz),
and collected for display and subsequent analysis using
a PowerLab data acquisition system (ADInstruments,
Sydney, New South Wales, Australia). At the end of the
experiments, the background noise level was determined
by hexamethonium bromide administration (30 mg/kg, i.v.,
Sigma-Aldrich). The neural activity was analyzed offline
using the Spike Histogram (ADInstruments) software. The
raw nerve signal was passed through a spike discriminator
to remove background noise, and the total nerve activity was
expressed in spikes per second (spikes/s).
Biochemical analyses
Superoxide dismutase (SOD) and glutathione peroxidase
(GPx) enzyme activities in the serum were determined using
RANSOD and RANSEL Kits (Randox Laboratories, Crumlin,
UK), respectively. Catalase (CAT) activity was assayed
according to Aebi, 1984 [13]. Lipid peroxidation was esti-
mated by serum levels of malondialdehyde [14]. The protein
concentration was measured by the Bradford method.
Reactive oxygen species in mesenteric arteries
The oxidation-sensitive fluorescent dye dihydroethidium
was used to evaluate the in-situ concentration of ROS in
mesenteric arteries, as previously described [15,16].
www.jhypertension.com 349
Garcia et al.
Nitric oxide production in mesenteric arteries
Nitric oxide production was determined in third-order
branches from mesenteric resistance arteries by use of
the 4,5-diamino fluorescein diacetate, an nitric oxide-
sensitive fluorescent dye, as previously described [17].
Composition of green tea by ultraperformance
liquid chromatography
We evaluated the composition of commercial green tea by
Ultraperformance Liquid Chromatography- Mass Spec-
trometry. An Acquity UPLC system (Waters Co., Milford,
Massachusetts, USA) consisting of a binary solvent manager
and a sample manager was coupled to an Acquity TQD
Mass Spectrometer (Micromass; Waters Co.). Analyses were
performed on a bridged ethylene hybrid C18 analytical
column (50 mm  2.1 mm, 1.7 mm), at a temperature of
258C, injecting 5 ml of green tea and standards. A gradient
was applied at a flow rate of 0.2 ml/min using two mobile
phases: purified water with 0.1% formic acid; and methanol
starting with 5% methanol , ramping to 100% methanol in
8 min, maintained until 8.50 min, returning to the initial
conditions. Detection was carried out in the negative
ion mode with an electrospray ionization source under
the following conditions: capillary 3000 V, cone 30 V,
temperature 1508C; ranging between m/z 1001000. Data
acquisition was carried out by Mass Lynx software (Waters
Co.). The green tea used in this study presented: 111 mg/ml
epigallocatechin, 210 mg/ml epigallocatechin gallate,
92 mg/ml epicatechin gallate, 15 mg/ml catechin, and
42 mg/ml epicatechin.
Statistical analysis
The results were expressed as the mean  SEM. All variables
were analyzed by one-way analysis of variance followed by
the Tukey post hoc test for specific intergroup differences.
A level of 5% probability was considered significant.
RESULTS
Cardiovascular parameters
L-Name-treated animals presented a significantly increased
MAP (165  2 mmHg, n 8) compared with CT rats
(103  1 mmHg, n 8), and green tea treatment signifi-
cantly reduced hypertension (119  1 mmHg, n 8)
(a)
200
* *
MAP (mmHg)
150
*#
100
50
0 0
T
C
+G
T+
H
C
FIGURE 1 Effects of GT treatment on (a) mean arterial pressure and (b) rSNA. , P < 0.05 compared with the CT group. #, P < 0.05 compared with the H group. CT,
control rats received only vehicle; GT, green tea; H, hypertensive rats treated with vehicle; MAP, mean arterial pressure; rSNA renal sympathetic nerve activity.
350 www.jhypertension.com
Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved.
(Fig. 1a). No differences in HR, water or tea intake, or
urinary volume were observed among groups (data not
shown).
The H group showed a significantly higher rSNA (Fig. 1b
161  12 spikes/s, n 7) than the CT group (97  2 spikes/
s, n 8). Green tea treatment significantly decreased rSNA
in the HGT group (125  5 spikes/s, n 6) and increased
this parameter in the CTGT group (124  5 spikes/s,
n 8).
The arterial baroreceptor reflex function is presented in
Fig. 2a and b, and the statistical data for the slopes are
shown in Table 1. The H group exhibited a pronounced
reduction in baroreflex sensitivity for both bradycardic
and tachycardic responses. Green tea treatment signifi-
cantly improved the arterial baroreceptor sensitivity
for the tachycardic response and completely restored the
bradycardic response in the HGT group.
Oxidative stress markers and antioxidant
enzyme activity
The values for serum SOD, CAT, and GPx activities are
shown in Fig. 3a,b and c, respectively. SOD and CAT
activity were increased in the H group compared with
those in the CT group. Green tea treatment normalized
these enzymes activity in the H group (Fig. 3a and b). GPx
activity was reduced in the H group, and green tea
treatment normalized the activity in HGT rats (Fig. 3c).
Figure 3d shows the MDA analysis. Lipid peroxidation in
the H group was significantly increased compared with that
in the CT group. Green tea treatment normalized this
parameter in the HGT group.
Reactive oxygen species production in
mesenteric arteries
As observed in Fig. 4a and b, DHE fluorescent intensity was
significantly increased in the H group, suggesting increased
ROS production. Green tea treatment significantly reduced
ROS levels in mesenteric arterioles. However, green tea
treatment did not alter ROS production in control animals.
Nitric oxide production in mesenteric arteries
At basal conditions, lower levels of nitric acid production
were detected in the mesenteric arterioles of both H and
HGT rats, suggesting that green tea treatment was not
(b)
200
rSNA (spikes/s)
150
* *#
100
50
T
+G
T+
H
Volume 35  Number 2  February 2017
 Green tea decreases sympathoexcitation

#* 200
(a) CT
CT+GT
H
H+GT

100
*

Depressor response
MAP (mmHg) 200 100 100 200
Pressor response

100

(b)
200
#
HR (bpm)
FIGURE 2 Effects of GT treatment on baroreflex function for (a) tachycardic and (b) bradycardic responses in the CT, CTgt, H, and HGT groups. See slope statistics in
Table 1. CT, control rats received only vehicle; GT, green tea; H, hypertensive rats treated with vehicle, HR, heart rate; MAP, mean arterial pressure.

effective in restoring nitric oxide bioavailability in this nitric with vitamin C, a nonenzymatic antioxidant, reduced renal
oxide inhibition hypertension model, Fig. 5a and b. oxidative stress, sympathetic activity, and BP [18]. Addition-
ally, microinjections of Tempol (a SOD mimetic) in regions
DISCUSSION of the brain involved with cardiovascular regulation
significantly reduced both BP and rSNA [19]. Such obser-
The major new findings of the present study were: green vations indicate that oxidative stress contributes to sympa-
tea treatment significantly reduced rSNA and improved thoexcitation in this model of renovascular hypertension.
arterial baroreceptor function leading to a reduction in In the present study, we also found an increase in rSNA,
BP, associated with decreased oxidative stress in hyper- which probably contributes to hypertension. Considering
tensive animals induced by nitric oxide synthesis inhibition. that rSNA potentially predicts BP [20], it is plausible that
Green tea treatment leads to a robust reduction of the reduction in sympathetic activity elicited by green tea
oxidative stress either vascularly or systemically in hyper- treatment in our study drives at least in part the decrease
tensive rats and our hypothesis is that the improvement in in BP. However, we cannot rule out the possibility that
cardiovascular and autonomic function induced by green other factors are also influencing this effect. Importantly,
tea is related to its antioxidant properties. Indeed, recently no alteration in urinary volume was observed with
the role of oxidative stress in the maintenance of hyperten- green tea treatment, excluding the possibility of a diuretic
sion has been extensively evaluated, and treatment with effect on BP.
antioxidant substances have been suggested to be poten- Interestingly, green tea increased rSNA with no change
tially beneficial for cardiovascular diseases [1,4,5]. Green tea in BP in the control group. In our interpretation, this is a
is a widely consumed beverage, and most of its beneficial reflex compensatory mechanism in response to green
effects in different situations are attributed to its antioxidant
effects. However, the role of its effects on BP is still
controversial. TABLE 1. Values of the slopes obtained from the linear
In the present study, green tea treatment promoted an regression graph of the function of baroreceptor
important 28% reduction in BP in hypertensive animals, reflex responses of heart rate (HR)
associated with a 22% reduction in rSNA and improvement Groups Tachycardic response Bradycardic response
in the arterial baroreceptor reflex control of BP. Sympath-
N Slope (bpm/mmHg) Slope (bpm/mmHg)
etic vasomotor hyperactivity is a key factor involved in the
generation of hypertension and is commonly observed in CT 8 3.74  0.19 2.47  0.07
humans and in experimental models [1,3]. Several studies CT GT 5 3.91  0.20 2.16  0.12
have correlated the reduction in oxidative stress with a H 5 0.82  0.13 1.36  0.11
H GT 8 2.80  0.13, 2.67  0.10
decrease in sympathetic activity leading to improvement in
BP [18,19]. Values are mean  standard error of the mean.
Previous studies by our group showed that in renovas- GT, green tea; HR, heart rate.

P < 0.05 compared with CT group.
cular hypertensive rats with high rSNA, chronic treatment 
P < 0.05 compared with H group.

Journal of Hypertension www.jhypertension.com 351

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Garcia et al.

(a) (b)
4 60 *
*

SOD (IU/mg protein)

CAT (IU/mg protein)

3
40

2 #
# * *
20
1

0 0
T

T
C

+G

+G
T+

T+
H

H
C

C
(c) (d)
0.05 5

MDA (g/mg protein)

GPx (IU/mg protein)

0.04 4 *

0.03 * 3 #

0.02 2

0.01 1

0.00 0
T

T
C

+G

+G
T+

T+
H

H
C

C
FIGURE 3 Effects of GT treatment on oxidative stress. Serum content of (a) SOD, (b) CAT, (c) GPx activities, and (d) MDA in the CT, CTGT, H, and HGT groups.

P < 0.05 compared with the CT group. #, P < 0.05 compared with the H group. CAT, catalase; CT, control rats received only vehicle; GT green tea; GPx,glutathione
peroxidase; H, hypertensive rats treated with vehicle; MDA malondialdehyde; SOD, superoxide dismutase.

tea preventing a decrease in BP. In an interesting study, humans or animal models. It has been suggested that
Barret et al. [21] described a sustained decrease in rSNA baroreflex dysfunction may also be involved in the gener-
after 1 week of hypertension induced by angiotensin II, ation of the hypertensive state [18]. Other antioxidants such
suggesting that baroreflex control of rSNA is likely to play a as resveratrol, quercetin, and vitamin C have been shown to
significant role in the control of arterial pressure not only in improve the baroreflex sensitivity in different models of
the short term but also in the long term. Thus, our interpret- hypertension [18,22,23]. The underlying mechanisms of
ation is that the increase in rSNA is a reflex long-lasting baroreflex dysfunction in hypertension are not very well
response to the reduction in BP induced by green tea. understood. However, reduction of oxidative stress, either
Another interesting result of the present study is the systemically or in the brain, seems to be related to the
pronounced improvement in the sensitivity of cardiac improvement of baroreflex sensitivity in pathological con-
baroreflex control in the hypertensive group after green ditions [18,22,23]. Although several studies correlate the
tea treatment. It is well known that baroreflex dysfunction is improvement in baroreflex with the reduction in the
a common feature observed in hypertension, either in oxidative state, it is also plausible that the improvement

(a) (b)
CT CT+GT
DHE fluorescence density

20 *
(arbitrary units)

15
ROS levels

10
H H+GT

0
T

T
C

+G
T+

H
C

FIGURE 4 (a) Digital images and (b) histogram illustrate the presence of ROS in DHE-treated sections of second branches of mesenteric arterioles. P < 0.05 H group
compared with CT, CTGT, HGT. CT, control rats received only vehicle; DHE, dihydroethidium; GT, green tea; H, hypertensive rats treated with vehicle; ROS, reactive
oxygen species.

352 www.jhypertension.com Volume 35  Number 2  February 2017

Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved.


(a)
CT CT+GT
DAF-2 fluorescence density
(arbitrary units)
NO levels
H H+GT
FIGURE 5 (a) Digital images and (b) histogram illustrate the presence of nitric oxide in DAF-2-treated sections of second branches of mesenteric arterioles. P < 0.05 H
group compared with CT and CTGT. #P < 0.05 H GT group compared with CT and CTGT. DAF-2, 4,5-diamino fluorescein diacetate; GT, green tea.
in the baroreceptor function was a consequence but not
a cause of reduction in BP.
Oxidative stress is an important player in the pathogen-
esis of hypertension and is commonly associated with
endothelial dysfunction and inflammation, which can
modify renal, vascular, brain, and cardiac function [4,5].
Antioxidants and anti-inflammatory therapies have been
the focus of several studies because of their potential to be
used as treatments for hypertension and other diseases.
In the present study, green tea promoted an improve-
ment in the antioxidant system, defined as the return of
antioxidant enzyme activity to the control group values
and by reducing lipid peroxidation. Although not exten-
sively evaluated, clinical studies described that green tea or
green tea components were associated with a reduction of
oxidative stress and BP [8,9].
The antioxidant defense system is composed of an
enzymatic and a nonenzymatic system. The enzymatic
system includes SOD, CAT, and GPx that work in coordi-
nation to convert superoxide anion to oxygen and water.
Briefly, it is known that SOD catalyzes the conversion of
superoxide anion to oxygen and hydrogen peroxide.
Hydrogen superoxide is in turn converted to water and
oxygen by CAT or GPx. In our study, we found an increase
in plasma SOD and CAT activities and a decrease in GPx
concentration in the L-NAME group. Although this model of
hypertension is characterized by an increase in ROS pro-
duction, it is likely that the increased SOD activity leads to
increased hydrogen peroxide formation. Although plasma
CAT activity is increased to scavenge hydrogen peroxide,
however, GPx activity is decreased in the hypertensive
group, indicating that the blockade of nitric acid synthase
results in a deficiency in the antioxidant defense system.
Interestingly, green tea treatment was efficient in improving
the antioxidant system and reducing ROS generation [24].
Catechins present in green tea exhibit antioxidant activity
by scavenging ROS, chelating redox-active transition
metal ions, inhibiting redox-sensitive transcription factors,
inhibiting prooxidant enzymes, and increasing antioxidant
activity [8].
It is known that the long-term inhibition of nitric oxide
synthesis alters endothelial function [2527]. It was dem-
onstrated that green tea is able to improve endothelial
function through several mechanisms based on their
Journal of Hypertension
Copyright 2017 Wolters Kluwer Health, Inc. All rights reserved.
Green tea decreases sympathoexcitation
(b)
20
15
10
#
5 *
T
C
+G
T+
H
C
antioxidant properties and the activation of endothelial
nitric oxide synthase (eNOS) [8,10,11,28]. Although the
beneficial effect of green tea treatment on the endothelial
dysfunction induced by nitric oxide blockade was not
directly investigated in the present study, the notion that
green tea affects the modulatory function of endothelial
cells could be supported by our findings. In fact, we show
here that ROS generation decreases in the mesenteric
artery after green tea treatment. This positive effect could
be attributed, at least in part, to an improvement in the
circulatory antioxidant profile. On the other hand, the oral
administration could also exert a local effect on the target
vascular system. Some investigations have found that green
tea polyphenols promoted a decrease of ROS production
because of downregulation of NADPH oxidase activity and
expression in the aortic rings [29]. Another study with
similar results found that treatment with green tea extract
was effective in preventing the increase in p22phox and
SOD mRNA in the aorta caused by angiotensin II infusion
[30]. However, further research is required to elucidate the
mechanisms involved in the beneficial effect of green tea on
the vascular ROS generated in our experimental model.
Despite its beneficial effects on ROS generation, green
tea did not increase nitric oxide synthesis in the current
study. There is strong evidence that green tea is able
to increase nitric oxide production by modulation of
eNOS activity through a PI3K/Akt/ cAMPprotein kinase
A-dependent mechanism [31,32]. Recently, an experimental
study found that the consumption of a diet rich in catechins
promoted increased eNOS activity, nitric oxide release,
and cGMP content. These authors observed that the
beneficial effect on the arterial tissues occurred independ-
ently of the alteration in the eNOS protein expression [31].
These discrepant results could be because of the vessel
types, the model of hypertension/stage of the disease, or
the green tea treatment regimen.
In summary, the present study describes an important
improvement in hypertension with only 1 week of green tea
treatment showing a very powerful action of this beverage.
Although the treatment duration was very short, the animals
were submitted to an exclusive tea intake that may have
potentiated the effect. Even so, green tea can be considered
to be a potential coadjuvant for the prevention or treatment
of hypertension. Moreover, the reduction in renal
www.jhypertension.com 353
Garcia et al.
sympathoexcitation suggests that green tea treatment is
beneficial in neurogenic forms of hypertension.
In conclusion, although it is known that green tea is a
potent antioxidant, our data show that green tea is effective
to target the mechanisms that lead to sympathoexcitation,
improving hypertension.
ACKNOWLEDGEMENTS
This study was supported by CAPES, CNPq, FAPESP (2013/
22522-9, 2010/09003-4). L.M.O., M.C.F., R.R.C. and C.T.B.
are recipients of CNPq fellowships.
Conflicts of interest
There are no conflicts of interest.
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Volume 35  Number 2  February 2017