Lin et al. BMC Complementary and Alternative Medicine (2016) 16:57
DOI 10.1186/s12906-016-1040-1

RESEARCH ARTICLE

Open AccessLong-term antihypertensive effects of
far-infrared ray irradiated from wooden
board in spontaneously hypertensive rats
Chien-Tsong Lin1,2, Ming-Ju Lin3, Yung-Pin Chen2, Ko-Chao Lee4, Kuo-Chin Huang5, Shun-Fu Chang6*
and Cheng-Nan Chen7*

Abstract
Background: Far-infrared ray (FIR) has been widely used in promoting health and has been shown to exert
beneficial effects in vascular function. The non-thermal effect of FIR has been found to play a significant role in theprotective effect on some vascular-related diseases, but its protective effects and use against hypertension have notbeen clearly presented.
Methods: In the present study, by using a wooden board coated with FIR-irradiated materials, we evaluated thelong-term antihypertensive effect on spontaneously hypertensive rats (SHRs) in the environment in contact with the
FIR-irradiated wooden board. SHRs were placed on the wooden board with or without FIR radiation for 4 weeks.
Results: The systolic blood pressure (BP) of SHRs undergoing different treatments was measured weekly using a
tail-cuff method. FIR radiation significantly reduced the systolic BP of the SHRs along with a decreasing plasma levelof angiotensin II and an increasing plasma level of bradykinin. In addition, long-term contact of FIR did not
significantly affect the BP in normotensive Wistar Kyoto rats (WKYs).
Conclusions: Our results provided the evidence based on which FIR radiation could be considered an effective
non-pharmacological choice for preventing hypertension.
Keywords: Angiotensin II, Far-infrared ray, Hypertension, Spontaneously hypertensive rats

Background
Hypertension, the persistent increase of blood pressure (BP)above 140/90 mmHg, is a major risk factor for the development of cardiovascular disease, including stroke, myocardial
infarction, heart and renal diseases, and cardiac mortality.
Although the etiology of hypertension is complex, therenin-angiotensin system (RAS) plays a major role in thepathology of hypertension [1, 2]. Renin catalyzes the conversion of angiotensinogen to angiotensin I, which is the ratedetermining step. Angiotensin-converting enzyme (ACE)then catalyzes the conversion of angiotensin I to angiotensin II, leading to the constriction of the arterial vessels and* Correspondence: sfchang@cgmh.org.tw; cnchen@mail.ncyu.edu.tw
6
Department of Medical Research and Development, Chang Gung Memorial
Hospital Chiayi Branch, No. 6, West Sec., Jiapu Rd., Puzi City, Chiayi County
613, Taiwan, ROC
7
Department of Biochemical Science and Technology, National Chiayi
University, Chiayi 600, Taiwan
Full list of author information is available at the end of the article

the regulation of systemic BP [3]. Since the increased
levels of angiotensin II are closely related to the development and maintenance of hypertension, the inhibition of angiotensin II formation has been widely
considered a major strategy for lowering BP in patientswith hypertension [4, 5]. Because sustained BP elevation may increase the incidence of atherosclerosis andstroke, it is important to develop alternative strategies for the treatment of hypertension.
The far-infrared ray (FIR) is generally defined as the electromagnetic wave in the wavelength range of 5.6–1000 μm.
FIR radiation has been widely applied to a variety of fields
as it has positive effects on food preservation [6], healthpromotion [7], and cardiovascular systems [8, 9]. Somestudies indicated that FIR therapy has potentially beneficial
effects in the treatment of wound healing [10], diabetes[11], tumor thermal therapy [12], chronic fatigue syndrome[13], and knee osteoarthritis [14]. In addition, several© 2016 Lin et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Lin et al. BMC Complementary and Alternative Medicine (2016) 16:57

studies also indicated that FIR radiation exerts beneficial
effects in the treatment of vascular diseases. FIR radiation
improved impaired vascular endothelial function in patientswith heart disease [15], decreased endothelial inflammation
by induction of heme oxygenase-1 [16], and augmented
angiogenesis in the ischemic hind limb [11]. These studies
revealed that the potential effects of FIR therapy played asignificant role in the protective effect on vascular function.
There is an increasing evidence that the secretion ofsoluble inflammatory makers play a significant role in
hypertension [17, 18]. Soluble intercellular adhesion
molecule 1 (sICAM-1), vascular adhesion molecule 1(sVCAM-1), and sE-selectin are major inflammatory
markers and endothelial cell adhesion molecules that
regulates the binding and extravasation of leukocytes
from the bloodstream to sites of inflammation [19].
The appearance of soluble inflammatory markers in thecirculation is thought to be the consequence of theirrelease from the vascular cells because of increased
expression [20].
The spontaneous hypertension rats (SHRs) are themost widely used animal model in the study ofhypertension-related diseases. The duration, cardiac
hypertrophy, renal dysfunction, and cardiovascularcomplications of SHRs are similar to those observedin human hypertension. In this study, by using thewooden board coated with FIR-emitting materials, weevaluated the long-term effect on SHRs in contact
with the FIR-emitting wooden board. Wistar Kyoto
rats (WKYs) were used as the control group. Thesefindings provide new insights into the treatment ofhypertension using FIR radiation.

Methods
The FIR-irradiated wooden board

All of the FIR-irradiated wooden board (53 × 21.5 × 1.5 cm;
length × width × thickness) samples used in this study weremade by Ua Wood Floors, Inc. (Yunlin, Taiwan). The
wooden boards were coated with Nano-paste (ZnO), which
was manufactured by Nano-Infinity Nanotech Co., Ltd.
(Taoyuan, Taiwan). Using the far-infrared ray testing system(Bruker, VERTEX 70 FT-IR) to test for far-infrared emissivity, the spectrums of the FIR-irradiated wooden board
exhibited high emissivity (>0.8) between 4 ~ 14 μm wavelengths (triplicate samples were made for each wooden
board, with measurements done by Industrial Technology
Research Institute in Taiwan).
Animal model

The study was performed in accordance with the guidelines for laboratory animals of National Chiayi University.
The protocol was approved by the Institutional Animal
Care and Use Committee of National Chiayi University.
All efforts were made to minimize suffering. Eight-

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week-old male SHRs and WKYs were obtained fromthe National Laboratory Animal Breeding and ResearchCenter of the National Science Council, Taiwan. All rats
were maintained five per cage at a constant temperature(24 ± 1 °C), with a 12-h dark/light cycle and a standard rat
chow diet. After the SHRs had been housed for 10 weeks,
their weight ranged from 240–250 g, and systolic BP
reached 180 mmHg. The rats were randomly divided into
four groups (n = 10 per group). Group 1: SHRs on awooden board without FIR radiation as the control group;group 2: SHRs on a wooden board with FIR radiation;group 3: SHRs on a normal wooden board with atenolol
administration as the positive control group; and group 4:
SHRs on an FIR-radiated wooden board with atenolol
administration. In addition, the WKY rats were divided into group 1 and group 2 for comparing theSHRs in this study.
Measurement of BP

BP was measured indirectly and non-invasively every
week by using the volume-oscillometric tail-cuff method(UR-5000, UEDA, Industries Co., Tokyo, Japan). To getan accurate BP, at least 7 consecutive determinations
were recorded. The maximum and minimum values of
BP were then eliminated, and the BP was calculated as
the average of the remaining values [21].
Analysis of plasma angiotensin II, bradykinin, and ACE
activity

After animal sacrifice, blood samples were collected
and kept on ice. The samples were collected and centrifuged at 3000 rpm for 15 min at 4 °C. The plasma
was stored at−80 °C until analysis. Both angiotensin
II and bradykinin were quantified by respective ELISA
kits (Angiotensin II ELISA, Cayman Chemical, Ann
Arbor, MI, USA; Bradykinin ELISA, Phoenix Pharmaceuticals, Burlingame, CA, USA) as per the manufacturers’ instructions. ACE activity was determinedaccording to the colormetric method using synthetic
sybstrate (FAPGG) [22]. One unit (U) of ACE acitvity
is defined as the amount of which released 1 μmol of
His-Leu per minute. The specific activity of ACE isexpressed as U/L.
Analysis of plasma inflammatory markers

The levels of sICAM-1, sVCAM-1, and sE-selectin inplasma were determined by using sandwich ELISA(R&D Systems, Minneapolis, MN) according to manufacturer’s protocols [23].
Statistics analysis

Data were reported as the mean ± standard error of themeans (SEM) and evaluated by one-way analysis of variance. Significant differences were established at P < 0.05.

Lin et al. BMC Complementary and Alternative Medicine (2016) 16:57

Results
FIR-irradiated wooden board attenuates BP in SHRs

The SHRs demonstrated already established hypertension at the beginning of the study (week 0). The resultsfrom this study, as illustrated in Fig. 1a, demonstrated
that at the start of the experiment, the mean values ofsystolic BP in all the SHRs were similar (174.5 to
179.6 mmHg). The systolic BP in the control SHRs wasincreased up to 193.6 mmHg at the end of the 4-weekperiod of experiment, whereas SHRs on an FIRirradiated wooden board started to reduce systolic BP
after 1 week, and this effect continued until the 4-weekexperimental period with gradual reduction in systolic
BP. Among the treatment, SHR administration withatenolol reduced the systolic BP more significantly atweek 3 and 4 compared with the SHRs treated with FIR

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only. There were no obvious changes in the systolic BP
in WKYs with or without FIR irradiation (Fig. 1b). Theseexperiments suggested that the effect of FIR irradiation
on SBP levels has specificity against hypertensive rats.
FIR irradiation inhibits plasma ACE activity in SHRs

Plasma ACE activity in the SHR untreated group was
significantly higher than in the WKY group (35.4 ± 3.1
vs. 124.5 ± 8.4 U/L). FIR irradiation decreased ACE
activity in the SHR untreated group to 76.7 ± 6.3 U/L in
the FIR-irradiated group (Fig. 2). In addition, SHR
administration with atenolol further reduced the plasma
ACE activity compared with the SHRs treated with FIR
only (Fig. 2).
FIR irradiation appears to inhibit angiotensin II in vivo

The effect of FIR irradiation on the systolic BP of the
SHRs was associated with concomitant changes in circulating levels of angiotensin II and bradykinin. FIR irradiation decreased angiotensin II levels from 48.2 ± 5.4 pg/
mL in the untreated group to 30.5. ± 3.1 pg/mL in the
FIR-irradiated group (Fig. 3). In addition, SHR administration with atenolol further reduced the angiotensin II
levels compared with the SHRs treated with FIR only
(Fig. 3). The treatment also increased the circulatinglevels of bradykinin (a molecule metabolized by ACE),
which increased from 1.82 ng/mL in the untreated group
to 3.05 ng/mL in the FIR irradiated group (Fig. 4). Moreover, the WKY rats had the lowest angiotensin II (Fig. 3)
and the highest bradykinin (Fig. 4) levels, compared to
all the SHR groups. These results suggest that FIR irradiation may decrease the production of angiotensin II as

Fig. 1 Changes in systolic BP of experimental rats during the 4-weekperiod. a The SHRs were randomly divided into four groups (n = 10
per group). Group 1: SHRs on a wooden board without FIR radiation
as the control group (control); group 2: SHRs on a wooden board
with FIR radiation (FIR); group 3: SHRs on a normal wooden board
with atenolol administration as the positive control group (atenolol);and group 4: SHRs on an FIR-radiated wooden board with atenolol
administration (FIR + atenolol). b The WKY rats were randomly
divided into two groups (n = 10 per group). Group 1: WKYs on awooden board without FIR radiation as the control group (control);and group 2: WKY rats on a wooden board with FIR radiation (FIR).
Data are mean ± SEM. *p < 0.05 vs. control SHRs, #p < 0.05 vs. SHRs
with FIR irradiation

Fig. 2 Plasma ACE activity of experimental rats after the 4-weektreatments. WKYs: WKYs on a wooden board without FIR radiation;
CL: SHRs on a wooden board without FIR radiation; FIR: SHRs on awooden board with FIR radiation; atenolol: SHRs on a normal
wooden board with atenolol administration; FIR + atenolol: SHRs on
an FIR-radiated wooden board with atenolol administration.
Data are mean ± SEM from n = 10 animals per treatment group.
*p < 0.05 vs. control SHRs, #p < 0.05 vs SHRs with FIR irradiation,†p < 0.05 vs. WKY group

Lin et al. BMC Complementary and Alternative Medicine (2016) 16:57

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WKY rats (Fig. 5). However, SHRs treated with FIR
showed decreased sICAM-1, sVCAM-1, and sE-selectinlevels compared to untreated group (Fig. 5).

Fig. 3 Plasma angiotensin II levels of experimental rats after the
4-week treatments. WKYs: WKYs on a wooden board without FIR
radiation; CL: SHRs on a wooden board without FIR radiation; FIR:
SHRs on a wooden board with FIR radiation; atenolol: SHRs on anormal wooden board with atenolol administration; FIR + atenolol:
SHRs on an FIR-radiated wooden board with atenolol administration.
Data are mean ± SEM from n = 10 animals per treatment group.
*p < 0.05 vs. control SHRs, #p < 0.05 vs SHRs with FIR irradiation,†p < 0.05 vs. WKY groupwell as inhibit the degradation of bradykinin, thereby
decreasing the systolic BP in SHRs.
FIR irradiation ameliorates plasma levels of inflammatory
markers

We further evaluated the effect of FIR irradiation on
plasma levels of sICAM-1, sVCAM-1, and sE-selectin in
SHRs. SHR untreated group exhibited an increase in
sICAM-1, sVCAM-1, and sE-selectin levels compared toFig. 4 Plasma bradykinin levels of experimental rats after the 4-weektreatments. WKYs: WKYs on a wooden board without FIR radiation;
CL: SHRs on a wooden board without FIR radiation; FIR: SHRs on awooden board with FIR radiation; atenolol: SHRs on a normal
wooden board with atenolol administration; FIR + atenolol: SHRs on
an FIR-radiated wooden board with atenolol administration. Data aremean ± SEM from n = 10 animals per treatment group. *p < 0.05 vs.
control SHRs, #p < 0.05 vs. SHRs with FIR irradiation, †p < 0.05 vs.
WKY group

Discussion
Recent findings showed that FIR radiation might play arole in the long-term protective effect on vascular function by reducing several cardiovascular risk factors suchas high BP. Our studies with FIR irradiation in SHRs
demonstrated for the first time that rats placed on FIR
irradiated wooden board indeed showed a systolic BP
reducing effect in the hypertensive rats in a timedependent manner. The FIR also decreased angiotensin
II and increased bradykinin production in the plasma of
the treated SHRs, suggesting the possible mechanisms for the systolic BP reducing effect of FIR.
Thus, FIR could prove to be a novel method for
management of hypertension.
SHRs are the animal model most frequently used toevaluate the in vivo antihypertensive effect of different
treatments such as drugs or dietary components. Various
studies performed to determine the antihypertensive
effects of food-derived bioactive peptides have used SHR
animals as a model system [24, 25]. To verify the validityof the experimental protocol, both a negative and apositive control group were included. The underlying
pathological mechanisms of the hypertensive effect in
SHRs include increased activity of the renin-angiotensin
system as well as increases in vascular inflammation andoxidative stress [26, 27]. Hence, SHRs are a suitablemodel to study the in vivo antihypertensive efficacy of
FIR irradiation. In the present study, systolic BP increased in the control SHR group during the 4-weekperiod of the study. In addition, the systolic BP was
significantly decreased in the positive control group(which received atenolol administration) when comparedto the negative control group. Thus, the negative andpositive control groups confirmed the validity of theanimal model chosen in this study.
The increase in BP is directly due to the vasoconstrictive actions of angiotensin II produced from angiotensin
I in the presence of ACE [28, 29]. Angiotensin II significantly increased the BP by the activation of angiotensin
II receptors in the vascular smooth muscle cells, resulting in increased vasoconstriction, decreased renal bloodflow and renal tubular sodium re-uptake, and increased
vasopressin secretion [30–32]. In our present study, FIR
radiation appears to act through angiotensin II, leading
to lowered BP in SHRs. FIR radiation reduced theplasma and angiotensin II levels with a corresponding
increase in bradykinin. The plasma levels of ACE activity
tended to be positively related to BP changes, which isconsistence with the earlier work that have shown thatACE levels could be used as a hypertension marker inLin et al. BMC Complementary and Alternative Medicine (2016) 16:57

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Fig. 5 Plasma sICAM-1 (a), sVCAM-1 (b), and sE-selectin (c) levels of experimental rats after the 4-week treatments. WKYs: WKYs on a wooden
board without FIR radiation; SHR-CL: SHRs on a wooden board without FIR radiation; SHR-FIR: SHRs on a wooden board with FIR radiation. Data
are mean ± SEM from n = 10 animals per treatment group. *p < 0.05 vs. WKY group, #p < 0.05 vs. SHRs with FIR irradiation

SHRs [33]. Our result is further confirmed by the factthat FIR-irradiated SHRs had significantly reductionof plasma ACE activity when compared to the untreated control, suggesting a role of elevated plasma
ACE activity in modulating hypertension conditions.
Thus, the antihypertensive effects of FIR radiation
may be mediated by downregulation of ACE with aconsequent reduction in the plasma levels of thevasoconstrictor angiotensin II.
It has been showed that FIR therapy has been applied to various clinical fields, particularly including
vessel-related disorders [34]. FIR radiation enhanced
blood flow retrieval and blood vessel formation inischemic hind limbs by enhancing the homing ofendothelial progenitor cells and lowering the oxidative
stress in ischemic tissue. Direct FIR radiation could
also ameliorate high-glucose-induced oxidative stress,
suppress cellular senescence, and improve endothelial
progenitor cell functions [11]. Although the mechanism
by which FIR radiation has a potential for the treatment ofvascular diseases is still unclear, the improvement of endothelial cell function is currently considered as a mechanism [35]. In addition, increasing evidence suggests FIR
therapy could exert beneficial effects in the cardiovascularsystem through the NO-related pathway [36]. FIR therapy
could upregulate eNOS expression and increase angiogenesis in an apolipoprotein E-knockout mouse model [37].
These findings suggest that FIR may provide somenovel rationales for its potential clinical impact on
vascular protection.
Vascular dysfunction or damage can be evaluated by
the measurement of inflammatory markers released
from vascular cells, such as sICAM-1, sVCAM-1, andsE-selectin [38]. Several studies have demonstrated thatthe plasma levels of inflammatory markers are increasedin patients with hypertension, type 2 DM, and atherosclerosis, all of which are well-established risk factors for
cardiovascular diseases [39–41]. Higher levels of soluble
inflammatory markers are associated with increased
cardiovascular risk in hypertension, presumably becausesuch high levels reflect chronic, low-grade vascularinflammation [18]. FIR therapy has been reported toexert a potent anti-inflammatory effect via induction of
HO-1 release by human umbilical vein endothelial cells[16]. Down-regulation in these markers may confer adecrease in cardiovascular risk, although prospective
data are needed to test this hypothesis. In the current
study, FIR irradiation decreased levels of the inflammatory markers sICAM-1, sVCAM-1, and sE-selectin,suggesting a specific anti-inflammatory property of FIR
in vivo. Since SHR untreated group has increased levelsof plasma inflammatory markers which may contributeto endothelial dysfunction, it is suggested that controlling the inflammatory responses with FIR irradiation
could potentially improve the vascular function andreduce inflammation.

Lin et al. BMC Complementary and Alternative Medicine (2016) 16:57

Conclusions
This study provides evidence of the antihypertensive
effect of FIR irradiation in SHRs. We found that thetreatment of SHRs with FIR irradiation induced adecrease in BP. Since FIR substantially decreased the
SHR plasma ACE activity and angiotensin II level, andincreased the bradykinin level, we believe that the mechanism of the antihypertensive effect of FIR on SHRs may
be related to the ACE inhibitory effect. Our results suggest
a possible beneficial effect of FIR on cardiovascular function and thus provide a mechanistic basis for the use of
FIR as an antihypertensive remedy in folk medicine.
Abbreviations
BP: blood pressure; RAS: renin-angiotensin system; ACE: angiotensin-converting
enzyme; FIR: far-infrared ray; SHR: spontaneous hypertension rat; WKY: Wistar
Kyoto rat.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
CTL, CNC, and SFC wrote the manuscript. CTL, CNC, and SFC designed
the study and performed the statistical analysis. MJL, YPC, KCL, and KCH
were involved in the acquisition of data. All authors read and approved
the final manuscript.
Acknowledgements
This study was supported by a grants from the Yunlin County Government,
Taiwan (102SBIR-A07), Chang Gung Memorial Hospital Chiayi Branch(CMRPG6E0231), and by the Ministry of Science and Technology, Taiwan(NSC101-2320-B-415-003-MY3, MOST103-2320-B182A-021-MY3).
Author details
1
Center for General Education, National Formosa University, Yunlin 632,
Taiwan. 2Department of Wood Based Materials and Design, National Chiayi
University, Chiayi 600, Taiwan. 3Department of physical Education, Healthand Recreation, National Chiayi University, Minsyong, Chiayi County 621,
Taiwan. 4Department of Colorectal Surgery, Department of Surgery, Chang
Gung Memorial Hospital; Kaohsiung Medical Cente, Kaohsiung 833, Taiwan.
5
Department of Orthopaedics, Chang Gung Memorial Hospital Chiayi Branch,
Chiayi 613, Taiwan. 6Department of Medical Research and Development,
Chang Gung Memorial Hospital Chiayi Branch, No. 6, West Sec., Jiapu Rd.,
Puzi City, Chiayi County 613, Taiwan, ROC. 7Department of Biochemical
Science and Technology, National Chiayi University, Chiayi 600, Taiwan.

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21.

Received: 7 October 2014 Accepted: 5 February 201622.
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