Acute effects of moderate-intensity cycling exercise on endothelial function in young healthy men: An investigation using the reactive hyperemia index

1. Introduction

The endothelium is believed to detect the initial stage of vascular dysfunction [1] and plays an important role in the prevention of cardiovascular disease. Among endothelial function tests, strain gauge plethysmography [23] is considered to best reflect endothelial function, but there are some disadvantages of using this modality, such as its invasive nature and long test duration. In contrast, flow-mediated dilation (FMD) [4] and reactive hyperemia-peripheral arterial tonometry (RH-PAT) [5] are simple, non-invasive methods with a short test duration and are therefore commonly used in clinical practice. According to precedent studies, FMD values can be improved by two weeks of exercise [6] or by 30 minutes of moderate-intensity acute exercise [7], and much evidence has been accumulated to link exercise and FMD. As for RH-PAT, less evidence has been established because its measurement device was developed later than the FMD measurement device. There have been reports that the reactive hyperemia index (RHI) obtained using RH-PAT can be used as a prognostic/predictive factor for cardiovascular events [8, 9] or as a useful index of endothelial function [5, 10]. In addition, compared to FMD values, RHI is less examiner-dependent [11] and is less likely to be influenced by the skill of the person who records the measurements. The difference between RH-PAT and FMD is that FMD is measured in the brachial artery, whereas RH-PAT is measured in the fingertip arterial bed. Therefore, it is necessary to establish evidence of relation between RH-PAT and exercising.

We hypothesized that the response of RH-PAT in exercise should differ from conventional indicators of endothelial function. In order to test the hypothesis, we examined the effects of acute aerobic exercise on vascular endothelial function using RH-PAT.

2. Materials and methods

A total of 27 healthy male college students selected as subjects were randomly divided into two groups: 14 in the exercise group and 13 in the control group. The subjects were given a written and verbal explanation of the objective, methods, safety, and other relevant information about this study, and signed a consent form after they thoroughly understood the content of the experiment. This study was approved as a “human subject research” by the Research Ethics Committee at Kansai University (approval no. 2018-03).

Prior to reactive hyperemia index (RHI) measurements, body size, pulse rate, and blood pressure were measured for each subject (Table 1). With reference to previous studies [12, 13], the subjects in the exercise group underwent 15 minutes of supine rest (PRE) followed by 30 minutes of cycling exercise (POST) and we measured RHI before and after exercise as an index of endothelial function. The subjects in the control group were instructed to have 40 minutes of rest, during which RHI was measured according to the same time schedule as in the exercise group. Measurements were recorded at least three hours after food and caffeine consumption in a quiet room with a temperature maintained at 24 ∘ C. In addition, the subjects were instructed to refrain from engaging in any strenuous physical activity for at least 12 hours prior to the time of measurement.

RHI was measured using Endo-PAT2000 (Itamar Medical Ltd., Caesarea, Israel). After 15 minutes of supine rest, pulse wave amplitudes were recorded with a pair of dedicated probes placed on the index finger of each hand for a total of 15 minutes, consisting of five minutes at rest, five minutes after inflating the pressure cuff placed around the left upper arm to 50 mmHg above the subject’s systolic pressure or 200 mmHg, whichever was higher, and five minutes after the release of blood flow occlusion. In the unilateral measurement, vasoconstriction resulting from sympathetic nerve stimulation by pain caused by blood flow occlusion and other factors may be included in reperfusion values. Therefore, we used the index finger on the non-occluded side as the control for comparison; RHI was calculated based on the dilation rate in the corresponding section on the control side, and by dividing the dilation rate on the occluded side by the dilation rate on the control side, the bilateral influence of the sympathetic nervous system was minimized.

3. Results

Regarding the subjects’ age, height, weight, body fat, pulse rate, and blood pressure, which are shown in Table 1, no significant differences were noted between the groups. For the comparison of reactive hyperemia index (RHI) between the two groups, two-factor analysis of variance showed a significant interaction effect ( P = 0.024, η p 2 = 0.188), and the simple main effect test showed a significant increase in RHI in the exercise group after exercise (PRE: 1.749 ± 0.308; POST: 2.302 ± 0.512; 0.001). However, no significant change was observed in the control group (PRE: 1.751 ± 0.535; POST: 1.842 ± 0.553; p = 0.517) (Fig. 1). In addition, no significant differences were observed in PRE RHI between the exercise and control groups ( p = 0.989), but POST RHI was significantly higher in the exercise group than in the control group ( p = 0.034).

OPEN IN VIEWER

In this study, we examined the effects of transient aerobic exercise on endothelial function in healthy college male students using reactive hyperemia-peripheral arterial tonometry (RH-PAT). As a result, reactive hyperemia index (RHI) was found to increase significantly after acute exercise.

In RH-PAT, measurements are performed in the digital arterial bed and the digital pulse volume is used as a parameter. For this reason, RH-PAT targets blood vessels with a diameter of 1 mm or less. While flow-mediated dilation (FMD) targets the brachial artery, RH-PAT evaluates the endothelial function of more peripheral and narrower blood vessels. According to studies published thus far, FMD values decrease immediately after smoking or following an oral glucose load [15, 16, 17, 18, 19, 20], but the RHI shows no change [21]. This suggests that the response of the endothelium to various stimuli may differ depending on the site of measurement. The same can be said based on its response to vasodilators. For example, nitric oxide (NO) is a vasodilator and plays a major role in dilating large blood vessels; however, as the vessel diameter becomes narrower, its role shifts to endothelium-derived hyperpolarizing factors [22, 23, 24, 25]. Therefore, the RH-PAT results may reflect not just NO [26] but other vasodilators as well.

Johnson et al. reported an improvement in FMD, an index of endothelial function, in young men after 30 minutes of moderate-intensity exercise [7]. Thus, exercising at moderate intensity for 30 minutes has been suggested to have a favorable impact on the vascular endothelium, which, in this study, was also found to be a useful stimulation to improve peripheral endothelial function. Outside this study, few studies have examined the relationship between endothelial function and exercise using RH-PAT. In terms of transient exercise, low-intensity stretching was reported to improve RHI [27]. In intervention studies, improved endothelial function has been demonstrated by exercising at moderate intensity according to one’s aerobic threshold [28] and low-intensity stretching [29], but there are no other reports. In terms of exercise intensity, our study and the abovementioned previous studies suggest that low to moderate exercise intensity may be useful in producing a favorable effect on peripheral endothelial function. With respect to FMD, which is used as a non-invasive tool for assessing endothelial function, it has been reported that increased exercise intensity is likely to produce greater effects on endothelial function [30]. However, since FMD and RH-PAT target different blood vessels, further investigation is necessary to determine whether the same phenomenon is seen with RH-PAT.

5. Conclusions

The results of this study reveal that 30 minutes of cycling exercise at moderate intensity can have a favorable impact on the endothelial function of peripheral blood vessels in the fingertips. Moreover, our findings may also serve as useful information for creating exercise prescriptions for patients with arteriosclerosis.