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Eur J Appl Physiol (2016) 116:749–757
DOI 10.1007/s00421-016-3328-8
ORIGINAL ARTICLE
Low‑intensity resistance training with blood flow restriction 
improves vascular endothelial function and peripheral blood 
circulation in healthy elderly people
Ryosuke Shimizu1 · Kazuki Hotta2 · Shuhei Yamamoto1,3 · Takuya Matsumoto4 · 
Kentaro Kamiya5 · Michitaka Kato1,6 · Nobuaki Hamazaki1,5 · Daisuke Kamekawa1 · 
Ayako Akiyama1 · Yumi Kamada1 · Shinya Tanaka1 · Takashi Masuda1 
Received: 12 April 2015 / Accepted: 27 December 2015 / Published online: 28 January 2016 
© Springer-Verlag Berlin Heidelberg 2016
The reactive hyperemia index (RHI), von Willebrand fac-
tor (vWF) and transcutaneous oxygen pressure in the foot 
(Foot-tcPO2) were assessed before and after the 4-week 
resistance training period.
Results Lac, NE, VEGF and GH increased sig-
nificantly from 8.2 ± 3.6 mg/dL, 619.5 ± 243.7 pg/
mL, 43.3 ± 15.9 pg/mL and 0.9 ± 0.7 ng/mL to 
49.2 ± 16.1 mg/dL, 960.2 ± 373.7 pg/mL, 61.6 ± 19.5 pg/
mL and 3.1 ± 1.3 ng/mL, respectively, in the BFR group 
(each P < 0.01). RHI and Foot-tcPO2 increased signifi-
cantly from 1.8 ± 0.2 and 62.4 ± 5.3 mmHg to 2.1 ± 0.3 
and 68.9 ± 5.8 mmHg, respectively, in the BFR group (each 
P < 0.01). VWF decreased significantly from 175.7 ± 20.3 
to 156.3 ± 38.1 % in the BFR group (P < 0.05).
Conclusions BFR resistance training improved vascular 
endothelial function and peripheral blood circulation in 
healthy elderly people.
Keywords Peripheral circulation · Reactive hyperemia · 
Low-intensity exercise · Hypoxia · Muscle strength · 
Neurohumoral factors
Abbreviations
BFR Blood flow restriction
eNOS Endothelial nitric oxide synthase
EPI Epinephrine
GH Growth hormone
NE Norepinephrine
NO Nitric oxide
RHI Reactive hyperemia index
RM Repetition maximum
tcPO2 Transcutaneous oxygen pressure
TM Thrombomodulin
VEGF Vascular endothelial growth factor
vWF von Willebrand factor
Abstract 
Purpose The present study aimed to investigate the 
effects of low-intensity resistance training with blood flow 
restriction (BFR resistance training) on vascular endothe-
lial function and peripheral blood circulation.
Methods Forty healthy elderly volunteers aged 
71 ± 4 years were divided into two training groups. Twenty 
subjects performed BFR resistance training (BFR group), 
and the remaining 20 performed ordinary resistance train-
ing without BFR. Resistance training was performed 
at 20 % of each estimated one-repetition maximum for 
4 weeks. We measured lactate (Lac), norepinephrine (NE), 
vascular endothelial growth factor (VEGF) and growth hor-
mone (GH) before and after the initial resistance training. 
Communicated by Fabio Fischetti.
 * Takashi Masuda 
 tak9999@med.kitasato-u.ac.jp
1 Department of Angiology and Cardiology, Kitasato 
University Graduate School of Medical Sciences, 1-15-1 
Kitasato, Minami-ku, Sagamihara 252-0373, Japan
2 Department of Biomedical Sciences, College of Medicine, 
Florida State University, 1115 West Call Street, Tallahassee, 
FL 32306, USA
3 Department of Rehabilitation, Shinsyu University Hospital, 
3-1-1 Asahi, Matsumoto 390-0862, Japan
4 Department of Rehabilitation, Kitasato University Kitasato 
Institute Hospital, 5-9-1 Shirokane, Minato-ku 108-8642, 
Japan
5 Department of Rehabilitation, Kitasato University Hospital, 
1-15-1 Kitasato, Minami-ku, Sagamihara 252-0375, Japan
6 Department of Shizuoka Physical Therapy, Faculty of Health 
Science, Tokoha University, Mizuochi, 1-30 Aoi-ku, 
Shizuoka 420-0831, Japan
750 Eur J Appl Physiol (2016) 116:749–757
1 3
Introduction
Supervised or home-based training programs are known 
to improve not only physical function but also quality of 
life in healthy elderly people (Schechtman et al. 2001). 
Resistance training is considered essential for maintaining 
their activities of daily living in these training programs, 
because it increases muscle strength more effectively than 
aerobic training (Pollock et al. 2000). Resistance training 
performed at a moderate to high-intensity workload has 
recommended to develop muscle strength in healthy adults 
(American College of Sports Medicine position stand 
2009). Indeed, it has been reported that more than 65 % of 
one-repetition maximum (1RM) is required as a workload 
for resistance training to increase muscle strength signifi-
cantly (McDonagh and Davies 1984). However, people suf-
fering from muscle and/or joint disorders often find it dif-
ficult to perform even moderate-intensity training as well as 
high-intensity training.
Recently, exercise training with blood flow restric-
tion (BFR) was reported to increase muscle strength in 
the extremities, and was performed by compressing the 
stem of upper or lower extremities using a pneumatic cuff 
(Loenneke et al. 2012). Previous studies have showed that 
hypoxic stress to skeletal muscles induced by exercise 
training with BFR increases muscle strength through the 
excessive secretion of neurohumoral factors such as lactate 
(Lac), norepinephrine (NE), vascular endothelial growth 
factor (VEGF) and growth hormone (GH) (Takarada et al. 
2000a ; Patterson et al. 2013). It is also known that exer-
cise training with BFR, performed even at low-intensity 
workloads, increases muscle strength in equivalent degrees 
to ordinary resistance training at a high-intensity work-
load (Takarada et al. 2000b). Furthermore, some studies 
have reported that muscle strength increases significantly 
in exercise training with BFR performed even for 4 weeks 
(Loenneke et al. 2012). Therefore, low-intensity exercise 
training with BFR is considered an effective means for 
increasing muscle strength, even for healthy elderly people 
(Ozaki et al. 2011).
With regard to vascular endothelial function, one mecha-
nism that improves the endothelial dysfunction is exercise 
training, which increases blood flow in skeletal muscles 
and enhances shear stress on vascular endothelial cells 
(Niebauer and Cooke 1996). Enhanced shear stress accel-
erates endothelial nitric oxide synthase (eNOS) expression, 
resulting in the amelioration of endothelial dysfunction in 
vessels of skeletal muscles (Green et al. 2004). Further-
more, hypoxic stress to vascular endothelial cells induced 
by exercise training with BFR reportedly increases eNOS 
expression via the activation of VEGF (Shweiki et al. 
1992; Patterson et al. 2013; Ziche et al. 1997), a mediator 
of angiogenesis. One study found that high-intensity aero-
bic exercise lowered tissue oxygen tension, which in turn 
upregulated VEGF mRNA expression in skeletal muscles 
(Breen et al. 1996). Another recent investigation demon-
strated that VEGF mRNA expression was accelerated in 
skeletal muscles 24 h after low-intensity resistance train-
ing with blood flow restriction (BFR resistance training) 
in healthy young subjects (Larkin et al. 2012). Further-
more, Hunt et al. showed that 4-week BFR handgrip train-
ing induced structural change in brachial artery indicating 
the enlargement of its diameter at rest (Hunt et al. 2012). 
Thus, low-intensity BFR resistance training is expected to 
serve as a useful means by which elderly people may not 
only increase muscle strength, but also enhance vascular 
endothelial function and peripheral blood circulation as 
well. However, it is still unknown whether or not low-inten-
sity BFR resistance training alleviates vascular endothelial 
dysfunction and increases peripheral blood circulation, 
although moderate to high-intensity resistance training 
without BFR has been known to improve them (Vona et al. 
2009).
The present study aimed to clarify the effects of 4 weeks 
of low-intensity BFR resistance training on vascular 
endothelial function and peripheral blood circulation in 
healthy elderly people.
Methods
This study was approved by theEthics Committee of Kita-
sato University, School of Allied Health Sciences. Written 
informed consent was obtained from all subjects after each 
received a detailed explanation of the study.
Subjects
Forty community-dwelling healthy elderly volunteers aged 
65 years or older (33 males and 7 females) were recruited 
for this study between April 2011 and March 2013. None 
of the subjects received outpatient care for any reason, and 
none had experienced any cardiovascular, cerebrovascular 
or neuromuscular disease. None of the subjects were smok-
ers, and none had any exercise habits including aerobic 
exercise, endurance training, resistance training, et cetera, 
for at least 6 months before the beginning of the study.
Subject characteristics
Subject age, sex, medication and orthopedic diseases his-
tory were examined by interview. We then measured their 
weight, height, blood pressure, fasting serum glucose, 
total cholesterol, high-density lipoprotein cholesterol, 
751Eur J Appl Physiol (2016) 116:749–757 
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low-density lipoprotein cholesterol and triglycerides, and 
calculated body mass index from their weight and height. 
We excluded subjects if they felt pain in the upper or lower 
extremities in activities of daily living. We also excluded 
any subjects who had received antihypertensive, hypolipi-
demic or hypoglycemic medications, or if they showed sys-
tolic blood pressure (SBP) ≥140 mmHg, diastolic blood 
pressure (DBP) ≥90 mmHg or abnormal blood examina-
tion results.
Study design
This study employed a randomized trial design. Subjects 
were initially divided into BFR resistance training (BFR) 
and non-BFR resistance training (non-BFR) groups using a 
randomized block method.
Study protocol
The study protocol consisted of (a) measurement of base-
line muscle strength, vascular endothelial function and 
peripheral blood circulation, (b) assessment of the acute 
effects of BFR resistance training, (c) conducting BFR or 
non-BFR resistance training for 4 weeks and (d) post-train-
ing measurement of the same parameters measured at base-
line. Acute effects of BFR resistance training were assessed 
at the initial resistance training session of the 4-week resist-
ance training period. All subjects performed 15-min resist-
ance training once a day, 3 days per week for 4 weeks. All 
measurements and resistance training were performed in 
a thermoneutral training room, which was maintained at 
22–24 °C and 40–60 % humidity.
BFR or non‑BFR resistance training
In the BFR group, four types of BFR resistance training, 
leg extension, leg press, rowing and chest press, were per-
formed each at 20 % intensity of estimated 1RM for bilat-
eral extremities in a seated or semi-reclined position using 
resistance training machines (COP-1202, COP-1201, COP-
0104 and COP-1101, respectively, SAKAI Medical, Tokyo, 
Japan). First, pneumatic cuffs (10 cm width) were attached 
to both proximal thighs, and subjects sat on the leg exten-
sion training machine. BFR was induced by inflating the 
cuffs to the same pressure as the subject’s femoral SBP 
using an inflator (Tourniquet 9000, VBM Medizintechnik 
GmbH, Sulz am Neckar, Germany). Subjects performed 3 
sets of leg extension training with the BFR, with each set 
consisting of 20 repetitions of leg extensions followed by 
30 s of rest. After leg extension training, they moved to 
the leg press training machine, wearing the cuffs which 
remained inflated, and rested on it for 1 min. They started 
leg press training using the same protocol as leg extension 
training. The cuffs were deflated and removed after sub-
jects finished the leg press training. Next, pneumatic cuffs 
(7 cm width) were attached to both proximal upper arms 
and inflated to the same pressure as their brachial SBP. The 
subjects performed rowing and chest press training, also 
using the same protocol as the lower extremity resistance 
training. The cuffs were never deflated during the training 
except when they were transferred from lower extremities 
to upper ones.
In the non-BFR group, subjects performed a series of 
resistance training without wearing cuffs.
Physical activity
Physical activity was assessed during the 4-week resist-
ance training period using an accelerometer (Lifecorder, 
SUZUKEN, Nagoya, Japan). The accelerometer, worn at 
the waist of each subject except during bathing and sleep-
ing, recorded vertical acceleration of the body. Energy 
expenditure was calculated using subject height, weight, 
sex and vertical acceleration. Physical activity was 
expressed in kcal/week (Kumahara et al. 2004).
Acute effects of resistance training
Changes in hemodynamic and neurohumoral parameters 
before and after resistance training were examined to 
assess the acute effects of BFR resistance training in the 
first training day. Heart rate (HR) and electrocardiogram 
(ECG) were continuously monitored throughout the ini-
tial resistance training using an ECG monitoring system 
(BSM-2401, NIHON KOHDEN, Tokyo, Japan). We meas-
ured HR, SBP, DBP, plasma concentrations of Lac, epi-
nephrine (EPI), NE and VEGF and serum concentration of 
GH before and immediately after the training.
Long‑term effects of 4‑week resistance training
Measurements of muscle strength, vascular endothelial 
function and peripheral blood circulation were assessed in 
the morning of the day before and the day after the 4-week 
resistance training period. All subjects were requested to 
refrain from eating and drinking (except for water) for 12 h 
before measurements.
Muscle strength
We assessed muscle strength with each type of resistance 
training using estimated 1RM testing, because an ordinary 
1RM measurement often induces hemodynamic instabil-
ity or skeletal muscle injuries in elderly subjects (de Vos 
et al. 2008; Pollock et al. 1991; Shaw et al. 1995). The 
estimated 1RM is calculated using the maximal number of 
752 Eur J Appl Physiol (2016) 116:749–757
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repetitions and submaximal weight. First, subjects lifted 
weights repeatedly as many as possible. If they were able 
to perform more than 10 repetitions, they repeated the same 
attempt using a heavier weight. When the maximum num-
ber of repetitions was 10 or fewer, the weight was consid-
ered a submaximal weight for the assessment of estimated 
1RM. Estimated 1RM was calculated as follows (Matt 
1993):
Previous studies have found that estimated 1RM has 
excellent interrater reliability for muscle strength measure-
ments (Abdul-Hameed et al. 2012). Therefore, the present 
study used estimated 1RM to assess muscle strength and 
determine the workload for resistance training.
Vascular endothelial function
The reactive hyperemia index (RHI) was measured in the 
supine position as a parameter of vascular endothelial func-
tion using a finger plethysmograph (Endo-PAT2000, Itamar 
Medical, Caesarea, Israel). The principle of RHI has been 
previously described (Rozanski et al. 2001). A blood pres-
sure cuff was placed on one of the upper arms with the con-
tralateral arm serving as a control, while fingertip probes 
were placed on both index fingers to measure arterial pulse 
wave amplitude. After a 5-min equilibration period, the 
cuff was inflated to either 60 mmHg above SBP or at least 
200 mmHg for 5 min. The cuff was then deflated to induce 
reactive hyperemia in the measured index finger, and the 
arterial pulse wave amplitude was recorded for 5 min. RHI 
was defined as the ratio of the arterial pulse wave ampli-
tude measured for 1 min during reactive hyperemia to the 
baseline amplitude during the equilibration period (Kuvin 
et al. 2003). RHI was automatically expressed after it was 
analyzed by a computerized automated algorithm, which 
was built into the device.
We also measured serum concentrations of von Wille-
brand factor (vWF) and thrombomodulin(TM) as param-
eters of vascular endothelial function and endothelial cell 
damage, respectively (Conway et al. 2003; Ishii et al. 
1991).
Peripheral blood circulation
Transcutaneous oxygen pressure (tcPO2) was measured 
as an indicator of peripheral blood circulation in the foot 
(Foot-tcPO2) using a tcPO2 device (PO-850, Sumitomo 
Electric Hightechs, Tokyo, Japan). After having subjects 
rest on a bed in the supine position for 20 min, we attached 
a probe heated to 44.8 °C to their first intermetatarsal 
Estimated 1RM (kg) = submaximal weight (kg)/
(102.78− 2.78×maximal number of repetitions)/100.
space on the dorsum of the right foot using the double-
sided adhesive ring supplied by the manufacturer. Five min 
after probe attachment, tcPO2 was recorded as stable if the 
value fluctuated within 2 mmHg during a one-min meas-
urement period. If the Foot-tcPO2 value measured after 
the resistance training period was higher than that of base-
line, peripheral blood circulation was defined as having 
improved relative to the baseline condition.
Blood examination
All blood samples were drawn from the brachial vein. 
Plasma Lac, EPI and NE, VEGF and vWF were measured 
by enzymatic method using lactate kit (Determiner LA, 
Kyowa Medex Co., Tokyo, Japan), HPLC using catecho-
lamine kit (CA test TOSOH, TOSHO CORPORATION, 
Tokyo, Japan), ELISA using human VEGF quantikine 
ELISA kit (DVE00, R&D systems, Minneapolis, USA) and 
aggregation method using vWF kit (BC von Willebrand fac-
tor reagent, Sysmex, Kobe, Japan), respectively. Serum GH 
and TM were assayed by electro-chemiluminescence immu-
noassay using human GH assay kit (Elecsys hGH, Roche 
Diagnostics Japan, Tokyo, Japan) and enzyme immunoas-
say using human TM assay kit (TM panacela plate, Daiichi 
Fine Chemical Co, Toyama, Japan), respectively.
Statistical analysis
A Shapiro–Wilk test was used to confirm normal dis-
tribution of the data. Natural log transformations were 
then performed to establish normality where necessary. 
An unpaired t test or χ2 test was used to compare differ-
ences in baseline characteristics between the two groups. A 
2-way repeated measures analysis of variance (ANOVA) (2 
groups versus 2 measurement points) was used to analyze 
differences in hemodynamic or neurohumoral parameters 
measured before and after the initial resistance training, as 
well as differences in muscle strength, vascular endothelial 
function and peripheral blood circulation before and after 
the 4-week resistance training period. If an F ratio was sig-
nificant, a post hoc test was performed using Bonferroni 
test. All values are expressed as mean ± standard deviation 
(SD), and a P value less than 0.05 was considered statisti-
cally significant. All analyses were performed using SPSS 
12.0J for Windows (SPSS Japan Inc., Tokyo).
Results
Subject baseline characteristics are displayed in Table 1. 
There were no significant differences in baseline character-
istics including physical activity between the two groups.
753Eur J Appl Physiol (2016) 116:749–757 
1 3
Acute effects of resistance training
Table 2 displays changes in hemodynamic and neuro-
humoral parameters before and after initial resistance 
training. There were no abnormal findings in HR and 
ECG during the training in all subjects. Significant inter-
actions were detected in HR, DBP, Lac, NE, VEGF and 
GH (F = 20.7, P < 0.01; F = 45.0, P < 0.01; F = 9.6, 
P < 0.01; F = 14.2, P < 0.01; F = 4.5, P < 0.05 and 
F = 39.7, P < 0.01, respectively). HR, SBP, DBP, Lac and 
NE increased significantly after initial training as com-
pared with before training in the two groups (P < 0.01 
for all in each group). In the BFR group, VEGF and GH 
increased significantly after initial training relative to 
before training (P < 0.01 for both), although they showed 
no significant changes before and after initial training in 
the non-BFR group. HR, SBP, DBP, Lac, NE, VEGF and 
GH after initial training were significantly higher in the 
BFR group than in the non-BFR group (P < 0.01 for all). 
There was no significant change in EPI before and after 
initial training in the two groups.
Long‑term effects of 4‑week resistance training
RHI, vWF and TM values before and after 4-week resist-
ance training are shown in Fig. 1a–c. A significant interac-
tion was detected in RHI (F = 10.8, P < 0.01) (Fig. 1a). 
RHI was significantly higher after 4-week resistance train-
ing than before training in the BFR group (P < 0.01). RHI 
after 4-week resistance training was significantly higher 
Table 1 Baseline 
characteristics
Data are expressed as mean ± SD
ns not significant, BMI body mass index, HR heart rate, SBP systolic blood pressure, DBP diastolic blood 
pressure, T-chol total cholesterol, HDL-C HDL cholesterol, LDL-C LDL cholesterol, TG triglyceride
Non-BFR group (n = 20) BFR group (n = 20) P value
Sex (male/female) 17/3 16/4 ns
Age (years) 70 ± 4 72 ± 4 ns
BMI (kg m−2) 22.9 ± 3.3 23.4 ± 2.5 ns
HR (bpm) 72 ± 15 70 ± 12 ns
SBP/DBP (mmHg)
 Brachial 132 ± 20/75 ± 18 134 ± 16/78 ± 15 ns
 Femoral 168 ± 22/115 ± 14 163 ± 17/120 ± 20 ns
Glucose (mg dL−1) 88.3 ± 10.5 84.7 ± 13.9 ns
T-chol (mg dL−1) 197.8 ± 26.6 198.5 ± 58.9 ns
HDL-C (mg dL−1) 57.5 ± 17.1 55.7 ± 11.4 ns
LDL-C (mg dL−1) 120.9 ± 17.3 124.2 ± 28.0 ns
TG (mg dL−1) 123.1 ± 35.7 113.9 ± 33.0 ns
Physical activity (kcal week−1) 12,180 ± 3733 13,114 ± 3252 ns
Table 2 Changes in 
hemodynamic and 
neurohumoral parameters 
before and after initial 
resistance training
Data are expressed as mean ± SD
HR heart rate, SBP systolic blood pressure, DBP diastolic blood pressure, Lac lactate, EPI epinephrine, NE 
norepinephrine, VEGF vascular endothelial growth factor, GH growth hormone
Interaction of * P < 0.05 and ** P < 0.01 (two groups versus two measurement points); †† P < 0.01 versus 
before; ‡‡ P < 0.01 versus Non-BFR group
Non-BFR group (n = 20) BFR group (n = 20)
Before After Before After
HR (bpm)** 68.1 ± 4.4 86.8 ± 6.1†† 71.6 ± 8.1 95.8 ± 11.7††,‡‡
SBP (mmHg) 135.7 ± 7.0 175.4 ± 15.4†† 137.6 ± 13.0 190.4 ± 27.2††,‡‡
DBP (mmHg)** 80.7 ± 6.9 86.5 ± 12.3†† 74.1 ± 4.4 107.6 ± 16.3††,‡‡
Lac (mg dL−1)** 10.3 ± 5.3 34.3 ± 13.3†† 8.2 ± 3.6 49.2 ± 16.1††,‡‡
EPI (pg mL−1) 62.2 ± 31.3 57.7 ± 36.6 50.1 ± 21.8 55.7 ± 33.7
NE (pg mL−1)** 472.4 ± 136.8 662.1 ± 201.5†† 619.5 ± 243.7 960.2 ± 373.7††,‡‡
VEGF (pg mL−1)* 43.2 ± 15.8 42.3 ± 19.5 43.3 ± 15.9 61.6 ± 19.5††,‡‡
GH (ng mL−1)** 0.9 ± 0.8 0.8 ± 0.7 0.9 ± 0.7 3.1 ± 1.3††,‡‡
754 Eur J Appl Physiol (2016) 116:749–757
1 3
in the BFR group than in the non-BFR group (P < 0.05). 
VWF decreased significantly after 4-week resistance 
training relative to that before training in the BFR group 
(P < 0.05) (Fig. 1b). TM showed no significant change with 
4-week resistance training in the BFR group (Fig. 1c), and 
RHI, vWF and TM showed no significant changes in the 
non-BFR group.
TcPO2 values before and after 4-week resistance 
training are shown in Fig. 2. A significant interaction 
was detected in tcPO2 (F = 16.8, P < 0.01). TcPO2 
increased significantly after 4-week resistance training 
relative to before training in the BFR group (P < 0.01), 
while no significant change was evident in the non-BFR 
group.
Muscle strength levels in leg extension, leg press, rowing 
and chest press before and after 4-week resistance training 
are shown in Table 3. Significant interactions were detected 
in leg extension, leg press and rowing (F = 5.1, P < 0.05; 
F = 11.7, P < 0.01; F = 5.7, P < 0.05, respectively). Esti-
mated 1RM of leg extension and leg press increased sig-
nificantly after 4-week resistance training relative to before 
in the BFR group (P < 0.01, and P < 0.01, respectively). No 
significant changes were observed in any estimated 1RM 
before and after 4-week resistance training in the non-BFR 
group.Fig. 1 Changes in RHI (a), vWF (b) and TM (c) before and after 
4-week resistance training. Open squares BFR group, closed squares 
non-BFR group. Data are expressed as mean ± SD. †P < 0.05 and 
††P < 0.01 versus before training; ‡P < 0.05 versus non-BFR group. 
RHI reactive hyperemia index, vWF von Willebrand factor, TM 
thrombomodulin. Before, before 4-week resistance training. After, 
after 4-week resistance training
Fig. 2 Change in tcPO2 before and after 4-week resistance training. 
Open squares BFR group, closed squares non-BFR group. Data are 
expressed as mean ± SD. ††P < 0.01 versus before training. tcPO2, 
transcutaneous oxygen pressure; before, before 4-week resistance 
training; after, after 4-week resistance training
Table 3 Changes in muscle 
strength before and after 4-week 
resistance training
Data are expressed as mean ± SD
1RM one-repetition maximum
Interaction of ** P < 0.01 and * P < 0.05 (two groups versus two measurement points); †† P < 0.01 versus 
before
Non-BFR group (n = 20) BFR group (n = 20)
Before After Before After
Estimated 1RM (kg)
 Leg extension* 51.0 ± 12.8 52.8 ± 13.9 46.8 ± 11.1 55.7 ± 16.7††
 Leg press** 145.1 ± 30.2 141.8 ± 33.0 138.7 ± 35.7 154.4 ± 36.8††
 Rowing* 43.1 ± 10.1 46.3 ± 10.4 41.4 ± 7.6 45.2 ± 10.2
 Chest press 35.1 ± 12.3 36.7 ± 12.2 34.7 ± 12.6 36.7 ± 12.1
755Eur J Appl Physiol (2016) 116:749–757 
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Discussion
A recent study found that low-intensity BFR resistance 
training induced muscle hypertrophy, yielding increased 
muscle strength in healthy young people (Loenneke et al. 
2012). The present study is the first report to demonstrate 
that low-intensity BFR resistance training improves vascu-
lar endothelial function and peripheral blood circulation, 
in addition to increasing muscle strength in healthy elderly 
people.
We found that RHI increased and vWF decreased sig-
nificantly after 4-week BFR resistance training. Because 
RHI and vWF mainly reflect nitric oxide (NO)-dependent 
endothelial function and endothelial cell damage in vessels, 
respectively, the increased RHI and decreased vWF indi-
cate that low-intensity BFR resistance training improved 
vascular endothelial function in healthy elderly people 
(Nohria et al. 2006; Conway et al. 2003). Exercise train-
ing at a moderate to high-intensity workload has been 
found to increase blood flow in skeletal muscles. Increased 
blood flow augments shear stress on vascular endothelial 
cells, resulting in improved endothelial function (Green 
et al. 2004). However, it is possible that BFR resistance 
training caused less shear stress due to low blood flow 
caused by cuff compression as compared with ordinary 
non-BFR resistance training (Takano et al. 2005). On the 
other hand, some have suggested that BFR resistance train-
ing may elicit hypoxic stress to tissues due to the reduced 
oxygen supply from low blood flow (Downs et al. 2014). 
Hypoxic stress reportedly accelerates VEGF release from 
cells in the vascular endothelium and skeletal muscles (Ji 
et al. 2007). VEGF bound to the endothelial cell membrane 
then upregulates eNOS expression, leading to increases in 
NO production (Hood et al. 1998; Strijdom et al. 2009). 
We also found that a single bout of BFR resistance train-
ing increased plasma concentrations of VEGF significantly 
relative to non-BFR resistance training. In addition, serum 
concentration of GH after a single bout of resistance train-
ing increased approximately threefold with BFR resistance 
training compared to non-BFR resistance training. GH has 
been reported to upregulate eNOS expression in endothe-
lial cells of human vessels or rat aorta (Thum et al. 2003; 
Wickman et al. 2002). Therefore, increased VEGF and 
GH from BFR resistance training are considered the main 
mechanisms underlying the improved vascular endothelial 
function.
With regard to peripheral blood circulation, the pre-
sent study demonstrated that Foot-tcPO2 increased signifi-
cantly after 4-week BFR resistance training. Because tcPO2 
reflects blood circulation in the skin microvasculature, 
our results suggest that BFR resistance training improved 
peripheral blood circulation in the foot. Long-term exer-
cise training is known to improve blood circulation in 
peripheral tissues by enhancing vascular endothelial func-
tion and angiogenesis (Stewart et al. 2002). Previous stud-
ies have clarified that enhanced endothelial function aug-
ments NO production from endothelial cells, resulting in 
increased regional blood flow (Niebauer and Cooke 1996). 
In addition, VEGF activated by hypoxic stress has been 
found to induce proliferation and migration of endothelial 
cells and accelerate angiogenesis in skeletal muscles and 
skin (Tammela et al. 2005; Detmar 2000). Therefore, we 
believe that 4-week BFR resistance training induced func-
tional and structural changes in peripheral vessels, which in 
turn improved peripheral blood circulation in the foot.
With regard to the acute effects of BFR resistance train-
ing, the present study showed that HR, SBP, DBP, NE 
and Lac measured after a single bout of resistance train-
ing were significantly higher in the BFR group than in the 
non-BFR group. Previous studies have clarified that BFR 
resistance training raises intracellular H+ concentrations 
in skeletal muscles followed by an increase in Lac, rela-
tive to that observed with non-BFR training (Fujita et al. 
2007; Suga et al. 2009). Increased H+ and Lac stimulate 
the chemosensors of skeletal muscles, which then activate 
the sympathetic nervous system during exercise training 
(Stebbins and Longhurst 1989). Therefore, we surmise that 
sympathetic nervous activity was more elevated during 
BFR resistance training than during non-BFR resistance 
training, because NE was significantly higher after train-
ing in the BFR group. This appears to be the main reason 
why HR and BP were elevated more following BFR resist-
ance training. However, a previous study showed that low-
intensity BFR resistance training induced fewer changes in 
intracellular H+ and metabolites in skeletal muscles rela-
tive to those induced by ordinary high-intensity resistance 
training (Suga et al. 2009). Because BP and HR depend 
on these metabolic changes during exercise training, from 
the perspective of preventing hemodynamic instability in 
elderly people while exercising, low-intensity BFR resist-
ance training may be safer to perform than high-intensity 
resistance training (Victor et al. 1988).
With regard to muscle strength, the present study 
showed that estimated 1RM in leg extension and leg press 
increased significantly after 4-week resistance training in 
the BFR group. However, their estimated 1RM was not 
significantly different from that of the non-BFR group. A 
recent report demonstrated that low-intensity BFR resist-
ance training effectively developed muscle hypertrophy and 
strength, while no effects were observed in ordinary low-
intensity resistance training (Loenneke et al. 2012). In addi-
tion, acidemia induced by high-intensity exercise training 
was found to augment GH secretion, also leading to mus-
cle hypertrophy (Gordon et al. 1994; Sutton et al. 1976; De 
Palo et al. 2001). The present study clearly demonstrated 
that low-intensity BFR resistance training significantly 
756 Eur J Appl Physiol (2016) 116:749–757
1 3
increased serum GH concentrations compared to non-BFR 
resistance training. Furthermore, acidemia accelerates 
neuromuscular adaptation resulting in increased muscle 
strength (Moritani et al. 1992). Therefore, the increase in 
muscle strength observed in the BFR group may have been 
derived from muscle hypertrophy or accelerated neuromus-
cular adaptation induced by these metabolic and neurohor-
monal changes.
There are some limitations to the present study. 
Eighty-three percent of thestudy subjects were male in 
the present study. The ratio of males to females might 
have affected the improvement of vascular endothe-
lial function, peripheral blood circulation and muscle 
strength in the present study. Therefore, further inves-
tigation is necessary to assess whether sex difference 
affects the improvement of them after the BFR resist-
ance training. We considered that hypoxic stress to skel-
etal muscles during BFR resistance training was one of 
underlying mechanisms to improve vascular endothelial 
function and peripheral blood circulation. We should 
investigate the effect of BFR without resistance train-
ing on them, because shear stress caused by reperfusion 
after BFR resistance training has been known to improve 
the endothelial dysfunction (Green et al. 2004). We sug-
gested that the 4-week BFR resistance training upregu-
lated eNOS expression resulting in the improvement of 
vascular endothelial function. However, we did not assess 
the eNOS expression in vascular endothelial cells in the 
present study. Therefore, further studies are needed to 
clarify whether the BFR resistance training upregulates 
eNOS expression using biopsied sample obtained from 
trained skeletal muscles (Miyauchi et al. 2003). We also 
suggested that the BFR resistance training improved 
peripheral blood circulation through the enhancement of 
vascular endothelial function and angiogenesis. However, 
we did not evaluate whether angiogenesis occurred in 
skeletal muscles. Therefore, it is necessary to clarify that 
the BFR resistance training increases capillary density in 
trained skeletal muscles (Hoier et al. 2012). Furthermore, 
we suggested that the BFR resistance training induced 
skeletal muscle hypertrophy resulting in the increase of 
muscle strength. Because we did not confirm the skeletal 
muscle hypertrophy in the present study, we should clar-
ify whether the BFR resistance training increases skeletal 
muscle volume by using magnetic resonance imaging in 
future studies (Abe et al. 2006).
In conclusion, low-intensity BFR resistance training not 
only increased muscle strength but also improved vascu-
lar endothelial function and peripheral blood circulation in 
healthy elderly people.
Acknowledgments This work was supported by JSPS KAKENHI 
Grant Number 26350585.
Compliance with ethical standards 
Conflict of interest The authors have no conflict of interest.
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	Low-intensity resistance training with blood flow restriction improves vascular endothelial function and peripheral blood circulation in healthy elderly people
	Abstract 
	Purpose 
	Methods 
	Results 
	Conclusions 
	Introduction
	Methods
	Subjects
	Subject characteristics
	Study design
	Study protocol
	BFR or non-BFR resistance training
	Physical activity
	Acute effects of resistance training
	Long-term effects of 4-week resistance training
	Muscle strength
	Vascular endothelial function
	Peripheral blood circulation
	Blood examination
	Statistical analysis
	Results
	Acute effects of resistance training
	Long-term effects of 4-week resistance training
	Discussion
	Acknowledgments 
	References

Outros materiais

Outros materiais