Introduction

High pulse pressure (PP) of the central arteries, such as the aorta and carotid artery, is more strongly associated with risk for cardiovascular disease than high PP of the peripheral arteries [1–4]. Thus, effective management of central arterial PP might be of pathophysiological importance. The pulsatile component of central arterial pressure consists of an incident wave elicited by left ventricular ejection and a late-arriving reflected wave arising from the peripheral vasculature of the lower body [5]. As the reflected wave seems to accrue at high resistance arterioles as well 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 caused by the administration of the endothelium-independent vasodilator nitroglycerin induces a significant reduction in the central augmentation index (AI), an index of wave reflection, without alterations in heart rate (HR) and blood pressure (BP) [6]. Additionally, systemic α1-adrenergic receptor blockade evokes a significant attenuation of aortic PP elevation during dynamic leg exercise [7]. Therefore, a transient 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 tone on central (carotid) arterial hemodynamics. To elicit vasodilation of the leg vasculature, we immersed the lower leg of eight healthy male subjects in a hot water bath as a heat treatment [8–12]; these subjects were considered to have 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 their respective medical history and did not take any medications. None of the participants had a history of smoking or regular physical exercise, and had adopted a normal living style. This study was approved by the Ethical Committees of the Institute of Health and Sport Sciences of the University of Tsukuba. 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 and vigorous 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 a temperature-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 and put 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 not containing hot water (control). To maintain the temperature of 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.

Measurements

Hemodynamic variables

Heart rate, brachial BP and pulse wave velocity (PWV) were measured with a vascular testing device equipped with an electrocardiogram, phonocardiogram, oscillometric extremities cuffs and an (optional) applanation tonometry sensor unit (Form PWV/ABI: Model BP-203RPEII 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 micropiezoresistive transducers. Briefly, PWV (=arterial path length/pulse transit time) was obtained between the carotid and femoral 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 a nonelastic tape measure [17]. Pulse transit times were automatically 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 the testing device (Fig. 1). The carotid AI was also calculated automatically as the pressure wave above its systolic shoulder, which was detected by fourth-order derivatives [15], divided by the PP [18]. Carotid arterial pressure was calibrated by equating the mean carotid and diastolic BP to the mean brachial and diastolic BP [19].

Fig. 1
figure 1

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

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Carotid blood pressure waveform analysis

LabVIEW-based pulse waveform analysis software (TRial, Omron Health Care Co., Kyoto, Japan) was used according 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 of variance (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 among mean 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 the heated lower leg also did not significantly from the control 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).

Table 1 Brachial arterial blood pressure, heart rate and body temperature responses to the heat intervention
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Fig. 2
figure 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

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Table 2 Carotid blood pressure, incident wave amplitude and parameters of wave reflection responses to the intervention
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Fig. 3
figure 3

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

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Discussion

Owing to the growing body of evidence demonstrating superior prognostic utility of central arterial PP compared with that of peripheral arterial PP [22–24], in the near future lowering the central arterial PP may become important in hypertension management and cardiovascular disease prevention. Therefore, we attempted to identify a determinant of the central arterial PP. A major finding of this study was that after the heat intervention the PWV in the lower leg did significantly decrease, and the reflected wave and central arterial PP did not change. This result suggests that the reduction in leg vascular tone induced by heating of 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 and reflected pressure waves along the arterial tree [5]. As the reflected pulse wave is likely to occur in the arterioles of the 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 and dampening the magnitude of the reflected pulse waves and subsequent 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 histamine receptor [12]. Thus, in order to reduce vasoconstrictor tone in the leg vasculature, we applied heat stimulation 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 and central (e.g. carotid artery) PP did not change significantly with heating of the lower leg. Although we were unable to clearly identify an etiology for this result, we do propose a number 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 the effects of heating an expanded full leg region, the use of different temperatures and/or the chronic application of lower leg heating on the central arterial PP are warranted.

Several methodological limitations of this study should be mentioned. First, we applied this method on carotid arterial pressure waveforms to extract carotid forward and backward 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 arterial pressure waveform differs from that of aorta, these are both classified 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 estimated from 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 to test our hypothesis. To gain insight into the physiological mechanisms 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 the influence of the transient reduction in leg vascular tone on the wave reflection and central arterial PP in healthy young men. 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.