J Physiol Sci (2015) 65:311–316
DOI 10.1007/s12576-015-0368-5

ORIGINAL PAPER

No influence of lower leg heating on central arterial pulse pressure
in young men
Keisei Kosaki • Jun Sugawara • Nobuhiko Akazawa •Koichiro Tanahashi • Hiroshi Kumagai •Ryuichi Ajisaka • Seiji Maeda

Received: 29 October 2014 / Accepted: 15 February 2015 / Published online: 27 February 2015
Ó The Physiological Society of Japan and Springer Japan 2015

Abstract Central arterial pulse pressure (PP), a strong
predictor of cardiovascular disease, mainly consists of anincident wave generated by left ventricular ejection and alate-arriving reflected wave emanating from the lower
body. We have tested the hypothesis that a reduction in leg
vascular tone by heat treatment of the lower leg attenuates
the central arterial PP. Pressure and wave properties of theperipheral and central arteries were measured in eight
young men before and after heat treatment of the lower leg(temperature approx. 43 °C) for 30 and 60 min, respectively. Following the lower leg heat trial, leg (femoral–
ankle) pulse wave velocity (PWV) was significantly decreased, but aortic (carotid–femoral) PWV and parametersof wave reflection and carotid arterial PP did not change
significantly. No significant changes were observed inthese parameters in the control trial. These results suggestthat the reduction in leg vascular tone induced by heat
treatment of the lower leg may not affect wave reflection
and central arterial PP in young men.

K. Kosaki  K. Tanahashi  H. Kumagai
Graduate School of Comprehensive Human Sciences, Universityof Tsukuba, Tsukuba, Ibaraki, Japan
J. Sugawara
Human Technology Research Institute, National Instituteof Advanced Industrial Science and Technology, Tsukuba,
Ibaraki, Japan
N. Akazawa  R. Ajisaka  S. Maeda (&)
Faculty of Health and Sport Sciences, University of Tsukuba,
1-1-1 Tennodai, Tsukuba, Ibaraki 305-8574, Japane-mail: maeda@taiiku.tsukuba.ac.jp
R. Ajisaka
Ministry of Health, Labour and Welfare, Tokyo, Japan

Keywords Central arterial pulse pressure  Reflectedwave  Pulse wave velocity  Lower leg heating

Introduction
High pulse pressure (PP) of the central arteries, such as theaorta and carotid artery, is more strongly associated withrisk for cardiovascular disease than high PP of the peripheral arteries [1–4]. Thus, effective management ofcentral arterial PP might be of pathophysiological importance. The pulsatile component of central arterial pressure
consists of an incident wave elicited by left ventricularejection and a late-arriving reflected wave arising from theperipheral vasculature of the lower body [5]. As the reflected wave seems to accrue at high resistance arterioles aswell as other sites of impedance mismatch in the arterial
tree (e.g., aortic bifurcation and branches of renal arteries)[5], it is very possible that peripheral vascular properties
influence central arterial PP. Systemic vasodilation causedby the administration of the endothelium-independent vasodilator nitroglycerin induces a significant reduction in thecentral augmentation index (AI), an index of wave reflection, without alterations in heart rate (HR) and bloodpressure (BP) [6]. Additionally, systemic a1-adrenergic
receptor blockade evokes a significant attenuation of aortic
PP elevation during dynamic leg exercise [7]. Therefore, atransient change in peripheral vascular tone may also alter
central arterial PP. Although the major reflected wave
emanates from peripheral vasculature in the lower body,the influence of regional change in leg vascular tone on
central arterial PP remains incompletely understood.
We have studied the influence of lower leg vascular toneon central (carotid) arterial hemodynamics. To elicit vasodilation of the leg vasculature, we immersed the lower

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leg of eight healthy male subjects in a hot water bath as aheat treatment [8–12]; these subjects were considered tohave relatively higher vasodilatory function [13, 14]. We
hypothesized that in these young men, decreased leg vascular tone due to heating of the lower leg would decrease
carotid arterial PP by the attenuation of wave reflection.
Methods
Subjects
We studied eight, apparently healthy young men [mean ±standard error of the mean (SEM): age 21 ± 1 years, height
171 ± 2 cm, weight 65 ± 2 kg]. All subjects had no apparent cardiovascular disease based on assessment of theirrespective medical history and did not take any medications.
None of the participants had a history of smoking or regularphysical exercise, and had adopted a normal living style.
This study was approved by the Ethical Committees of theInstitute of Health and Sport Sciences of the University ofTsukuba. The study conformed to the principles outlined in
the Helsinki Declaration, and all subjects provided written
informed consent before inclusion in the study.
Experimental protocol
The experiment consisted of a 30-min intervention (lower leg
heating and control) and pre- and post-intervention hemodynamic measurements, with the post-intervention measurements performed 30 and 60 min after the intervention.
The subjects abstained from alcohol, caffeine intake andvigorous exercise for at least 24 h before the experiments. In
all experiments, the subjects were evaluated concurrently.
First, they were asked to lay still for at least 30 min in atemperature-controlled room (approx. 23 °C) before baseline
measurements were obtained. Then, during the interventions,the subjects were asked to rest still in a comfortable chair andput their lower legs and feet into a plastic bucket (diameter
42 cm, depth 40 cm) containing hot water (approx. 43 °C,
approx. 40 cm of hot water; lower leg heating trial) or notcontaining hot water (control). To maintain the temperatureof the water in the plastic basin at 43° for 30 min, hot water(at 43°) was continually added to the bucket during the
30-min trial using a hot-water supply system (BC60V3;
Rinnai Corporation, Nagoya, Japan). These trials were performed on separate days with a crossover design.

J Physiol Sci (2015) 65:311–316

with an electrocardiogram, phonocardiogram, oscillometric extremities cuffs and an (optional) applanation
tonometry sensor unit (Form PWV/ABI: Model BP203RPEII and TU-100; Colin Medical Technology,
Komaki, Japan), as previously described [15, 16]. Carotid and femoral arterial pressure waveforms were simultaneously recorded by two applanation tonometry
sensors incorporating an array of 15 micropiezoresistivetransducers. Briefly, PWV (=arterial path length/pulse
transit time) was obtained between the carotid andfemoral regions (e.g. aorta) and between the femoral
and ankle regions (e.g. leg). These arterial path lengths
were assessed in duplicate with a random zero length
measurement over the surface of the body with anonelastic tape measure [17]. Pulse transit times wereautomatically computed from simultaneously recorded
arterial pressure waveforms at the left carotid, left
femoral (via applanation tonometory sensors) and left
posterior-tibial (via air plethysmography) arteries by the
5- to 30-Hz band pass filter-based algorithm of thetesting device (Fig. 1). The carotid AI was also
Table 1 Brachial arterial blood pressure, heart rate and body temperature responses to the heat intervention
Variables

Baseline

Post-intervention:
30 minPost-intervention:
60 minBrachial SBP (mmHg)
Control

114 ± 1114 ± 2116 ± 2Lower legheating

114 ± 2114 ± 2113 ± 2Brachial MBP (mmHg)
Control

81 ± 183 ± 284 ± 1

Lower legheating

83 ± 183 ± 285 ± 2Brachial DBP (mmHg)
Control

61 ± 162 ± 264 ± 2Lower legheating

62 ± 262 ± 362 ± 2HR (beats/min)
Control

54 ± 252 ± 253 ± 2Lower legheating

58 ± 258 ± 358 ± 2Axillary temperature (°C)
Control

36.3 ± 0.1

36.5 ± 0.1

36.3 ± 0.1

Lower legheating36.7 ± 0.1

36.7 ± 0.1

36.6 ± 0.1

Tympanic temperature (°C)

Measurements

Control

36.6 ± 0.2

36.6 ± 0.2

36.7 ± 0.2

Lower legheating37.3 ± 0.2

37.4 ± 0.2

37.3 ± 0.2

Hemodynamic variables

Data are presented as the mean ± standard error of the mean (SEM)

Heart rate, brachial BP and pulse wave velocity (PWV)
were measured with a vascular testing device equipped

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SBP Systolic blood pressure, MBP mean arterial pressure, DBP diastolic blood pressure, PP pulse pressure, HR heart rate

J Physiol Sci (2015) 65:311–316

313

Fig. 1 Sample of simultaneousrecordings of electrocardiogram(ECG), phonocardiogram(PCG) and arterial pressure
waveforms at carotid (CAP),
brachial (BAP), femoral (FAP),
and posterior–tibial (PAP)
arteries by an automatedpolygraph apparatus. Each box
above the carotid arterial
waveform indicates the locationof tonometry sensor which
detected the strongest pressure(black bar) among 15 sensors

calculated automatically as the pressure wave above its
systolic shoulder, which was detected by fourth-orderderivatives [15], divided by the PP [18]. Carotid arterialpressure was calibrated by equating the mean carotid
and diastolic BP to the mean brachial and diastolic BP[19].
Carotid blood pressure waveform analysis
LabVIEW-based pulse waveform analysis software(TRial, Omron Health Care Co., Kyoto, Japan) was usedaccording to the algorithm published by Westerhof et al.
[20] and Qasem and Avolio [21] to decompose the carotid
arterial pressure waveforms into the forward- and backward-traveling (incident wave and reflected wave, respectively) waves and their time delay [e.g. the return time of
the reflected wave (TR)].

Statistical analyses
The effects of acute lower leg heating on hemodynamic
variables were evaluated by repeated-measure analysis ofvariance (ANOVA) in a general linear model (GLM). In
the case of a significant F value, Fischer’s LSD post hoc
test was used to identify significant differences amongmean values. All data were reported as mean ± SEM.
Statistical significance was defined a priori at P \ 0.05.

Results
Brachial arterial BP, HR and body temperature in the lower
leg subjected to heating and in the control lower leg were
not significantly different (Table 1). The aortic PWV in theheated lower leg also did not significantly from the control

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J Physiol Sci (2015) 65:311–316
Table 2 Carotid blood pressure, incident wave amplitude and parameters of wave reflection responses to the intervention
Variables

Baseline

Post-intervention:
30 minPost-intervention
60 minCarotid SBP (mmHg)
Control

109 ± 2106 ± 2108 ± 1

Lower legheating

114 ± 2113 ± 3109 ± 3

Carotid DBP (mmHg)
Control

61 ± 162 ± 165 ± 2Lower legheating

62 ± 262 ± 362 ± 2Control

47.7 ± 2

44.1 ± 2

44.6 ± 3

Lower legheating50.8 ± 3

48.3 ± 546.2 ± 3

Control

14.3 ± 1

14.4 ± 1

13.9 ± 1

Lower legheating

13.4 ± 1

13.4 ± 1

13.0 ± 1

Control

152 ± 5146 ± 5152 ± 5Lower legheating

151 ± 4141 ± 6146 ± 5Control-27.8 ± 4

-20.7 ± 4-22.1 ± 4

Lower legheating-33.6 ± 6-25.8 ± 6

-21.3 ± 6

IWA (mmHg)

RWA (mmHg)

TR (ms)Carotid AI (%)

Fig. 2 Responses of aortic (top) and leg (bottom) pulse wave velocity
to the heating intervention. Data are given as the mean ± standard
error of the mean (SEM). *P \ 0.05 vs. baseline

level (Fig. 2). Leg PWV was significantly decreased at
30 min after the lower leg heating trial (773 ± 30 vs.
741 ± 26 cm/s, respectively; P \ 0.05), and this decrease
was not observed after the control trials (Fig. 2). Carotid
BP, incident wave amplitude and parameters of wave reflection, such as AI, TR, and reflected wave amplitude, did
not change significantly in either the lower leg heating trial
or control trial (Table 2). Carotid and brachial arterial PP
did not change significantly throughout both trials (Fig. 3).

Discussion
Owing to the growing body of evidence demonstratingsuperior prognostic utility of central arterial PP comparedwith that of peripheral arterial PP [22–24], in the near future lowering the central arterial PP may become importantin hypertension management and cardiovascular disease
prevention. Therefore, we attempted to identify a determinant of the central arterial PP. A major finding of this123

Data are presented as the mean ± SEM
IWA Incident wave amplitude, RWA reflected wave amplitude, TRtiming of reflected wave, AI augmentation index

study was that after the heat intervention the PWV in thelower leg did significantly decrease, and the reflected wave
and central arterial PP did not change. This result suggeststhat the reduction in leg vascular tone induced by heatingof the lower leg does not affect the wave reflection and,
consequently, does not affect the central arterial PP in
young men.
The central arterial PP differs from the peripheral arterial PP due to the variable superposition of incident andreflected pressure waves along the arterial tree [5]. As thereflected pulse wave is likely to occur in the arterioles ofthe lower body, which show high resistance, as well as at
the aortic bifurcation and branches of the renal arteries [5],we assumed that heating of the lower leg would reduce leg
vasoconstrictor tone, resulting in delayed return anddampening the magnitude of the reflected pulse waves andsubsequent attenuation of the central arterial PP.
It is well-known that warmth stimulation elicits vasodilatory substances, such as nitric oxide [10, 11], vasoactive intestinal peptide [8], prostanoids [9] and H1

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Fig. 3 Responses of brachial (top) and carotid (bottom) arterial pulsepressure to the intervention. Data are reported as the mean ± SEM

histamine receptor [12]. Thus, in order to reduce vasoconstrictor tone in the leg vasculature, we applied heatstimulation to both of the lower legs of young healthy men
who were likely to have relatively higher vasodilatory
function. As expected, we found that heating of the lower
leg decreased leg PWV, presumably due to a reduced local
vasoconstrictor tone. However, aortic PWV, RWA andcentral (e.g. carotid artery) PP did not change significantlywith heating of the lower leg. Although we were unable toclearly identify an etiology for this result, we do propose anumber of theories. First, since the major reflection site is
located in the abdominal region (i.e., renal and aortic bifurcation) in young adults [25], a reduction in the leg
vasoconstrictor tone might not affect central arterial hemodynamics. In this context, an investigation of elderly
adults may clarify whether this proposal is valid because
the major wave reflection site shifts distally with advancing
age [25]. Alternatively, the region subjected to heating (e.g.
lower legs) might have been too small to influence central
arterial hemodynamics. Further studies investigating the315

effects of heating an expanded full leg region, the use ofdifferent temperatures and/or the chronic application oflower leg heating on the central arterial PP are warranted.
Several methodological limitations of this study shouldbe mentioned. First, we applied this method on carotid
arterial pressure waveforms to extract carotid forward andbackward pressure components, as previously reported[26]. The Westerhof’s triangulation method had been
proposed for decomposing aortic forward and backward
pressure waves. Although the shape of carotid arterialpressure waveform differs from that of aorta, these are bothclassified as central arterial pressure and provide qualitatively similar clinical information [27]. Of note, to validate
this approach, we compared the ratio of backward pressure
wave amplitude to forward pressure wave amplitude obtained from the carotid arterial waveform and found that
this ratio was strongly correlated with the corresponding
value acquired from aortic waveforms that was estimatedfrom simultaneously recorded radial arterial pressure
waveforms (r = 0.758, P \ 0.01). Second, we performed
measurements at 30 min post-intervention to elicit the reduction in local (leg) vasoconstrictor tone without systemic
hemodynamic change (i.e. peripheral BP and HR), as seen
in a previous study investigating the acute effect of aerobic
exercise [28]. This protocol was likely the preferable one totest our hypothesis. To gain insight into the physiologicalmechanisms of central arterial hemodynamics, measurements of leg vascular tone at an earlier post-intervention
phase (\30 min) are warranted.
In summary, using lower leg heating, we determined theinfluence of the transient reduction in leg vascular tone on
the wave reflection and central arterial PP in healthy youngmen. Despite the decrease in leg PWV, measures of wave
reflection and carotid arterial PP did not change significantly following the lower leg heating intervention.
These results suggest that the lower leg heating-induced
reduction in leg vascular tone does not affect the wave
reflection and central arterial PP in young men.
Acknowledgments We thank Mr. Satoshi Oikawa for his technicalassistance. The pulse waveform analysis software used for the present
study was provided by Omron Health Care Corporation.
Conflict of interest

None.

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