The physiological and perceptual data from the exercise trials are presented in Table 3. All participants completed both exercise trials. The highest V˙O2 achieved during the HIIE condition equated to 96% ± 5%. The average length of the MIE trial was 25.8 ± 2.1 min. Nine boys and eight girls indicated that they preferred the HIIE exercise bout.
Baseline arterial diameter, SRAUC, and FMD are illustrated in Figure 1. A time–trial interaction was present for FMD (P < 0.001). No differences in mean FMD at baseline were apparent between trials (P = 0.62; 95% CI, −1.2 to 0.7; ES = 0.12). Compared with that in baseline, FMD was attenuated immediately after HIIE (P < 0.001; 95% CI, −4.4 to −2.3; ES = 1.20) but was unchanged immediately after MIE (P = 0.28; 95% CI, −1.5 to 0.4; ES = 0.26). Consequently, FMD was lower in HIIE compared with that in MIE immediately after exercise (P < 0.001; 95% CI, −3.4 to −1.6; ES = 1.57). FMD was not different from baseline 1 h (P = 0.67; 95% CI, −0.8 to 1.2; ES = 0.10) and 2 h (P = 0.72; 95% CI, −0.8 to 1.1; ES = 0.08) after MIE; however, FMD was greater than baseline after HIIE at these time points (P < 0.001; 95% CI, 1.7–3.7; ES = 1.33; and P < 0.001; 95% CI, 1.8–3.7; ES = 1.36, respectively). Consequently, FMD was greater in HIIE compared with that in MIE 1 h (P < 0.001; 95% CI, 1.8–3.8; ES = 1.31) and 2 h (P < 0.001; 95% CI, 1.8–3.8; ES = 1.33) after exercise. Changes in FMD after exercise were not related to age, maturity (Tanner stage), or aerobic fitness in either MIE or HIIE (r < 0.43 and P > 0.10 for all).
There was a main effect of time (P < 0.001), but not trial (P = 0.28), or time–trial interaction (P = 0.75) for SRAUC. Pairwise comparisons revealed that SRAUC was elevated immediately after exercise compared with that at baseline in MIE (P < 0.001; 95% CI, 206–564; ES = 1.20) and HIIE (P = 0.001; 95% CI, 205–704; ES = 1.31). There was also a trend for SRAUC to be greater 1 h after MIE (P = 0.06; 95% CI, −10 to 358; ES = 0.55) and HIIE (P = 0.08; 95% CI, −27 to 394; ES = 0.64) compared with that in baseline. SRAUC was not different from baseline 2 h after exercise for either trial (P > 0.14, ES < 0.36 for both).
There was a main effect of time (P < 0.001), but not trial (P = 0.68), or time–trial interaction (P = 0.09) for baseline arterial diameter. Baseline arterial diameter was greater immediately after exercise compared with preexercise values in MIE (P = 0.03; 95% CI, 0.01–0.22; ES = 0.32) and HIIE (P = 0.01; 95 CI, 0.05–0.35; ES = 0.51). Baseline diameter was not different from preexercise values at any other point in either trial (P > 0.21, ES < 0.20 for all).
Differences in parameters of microvascular function are presented in Figure 2. There was a main effect of trial (P = 0.002) and time (P < 0.001) for PRH but no time–trial interaction (P = 0.14). There were no differences between trials in mean PRH at baseline (P = 0.51; 95% CI, −0.18 to 0.09; ES = 0.12). Compared with that at baseline, PRH increased immediately after MIE (P = 0.048; 95% CI, 0.02–0.46; ES = 0.72) and HIIE (P < 0.001; 95% CI, 0.26–0.61; ES = 1.16). PRH was greater in HIIE compared with that in MIE immediately after (P = 0.02; 95% CI, 0.05–0.44; ES = 0.73) and 1 h after exercise (P = 0.002; 95% CI, 0.13–0.48; ES = 0.67). There was also a trend for PRH to be greater in HIIE 2 h after exercise (P = 0.08; 95% CI, −0.03 to 0.42; ES = 0.43).
There was a main effect of trial (P = 0.01) and time (P < 0.001) for the total hyperemic response but no time–trial interaction (P = 0.17). There were no differences in total hyperemic response between trials at baseline (P = 0.65; 95% CI, −28 to 18; ES = 0.12). Compared with that at baseline, the total hyperemic response was greater at all times after MIE (P < 0.02 and ES > 0.60 for all) and HIIE (P < 0.001 and ES > 1.18 for all). The total hyperemic response was greater in HIIE compared with that in MIE immediately after (P = 0.03; 95% CI, 3–57; ES = 0.67) and 1 h after exercise (P = 0.01; 95% CI, 12–72; ES = 0.62), with a strong trend for a statistical difference 2 h after exercise (P = 0.06; 95% CI, −1 to 56; ES = 0.45).
The purposes of this investigation were to establish the effect of exercise intensity on macro- and microvascular functions in adolescents and to document the time course of the response. The novel findings from this study are as follows: compared with baseline, 1) FMD was attenuated immediately after a single bout of HIIE but not after MIE, 2) FMD was elevated 1 and 2 h after HIIE but was unchanged in MIE, 3) PRH and total hyperemic response are both increased during the 2 h immediately after MIE and HIIE and the magnitude of this increase is greater after HIIE than that after MIE. This is the first study to isolate the effect of exercise intensity and include serial measures of vascular function in adolescents after a single bout of exercise. The findings indicate that exercise intensity has an independent effect on macro- and microvascular functions in young people, which likely have important implications for vascular health.
Our data demonstrate that an immediate postexercise nadir in FMD is present after HIIE but not after MIE, which is consistent with work-matched data in adults (3,183,18) and the only available data in young people (22). Mills et al. (22) hypothesized that this attenuation in FMD after high-intensity exercise might precede an increase in FMD and therefore be considered to be beneficial. However, these authors did not include serial measures of FMD in their investigation, and evidence of this response in endothelial function after exercise is scarce (18). Furthermore, the “high-intensity” exergaming trial included by Mills et al. (22) elicited a peak V˙O2 of 3.6 ± 2.5 METs, which the authors correctly classified as moderate intensity (24). Therefore, the present study extends the work by Mills et al. (22) and, to our knowledge, is the first to confirm that the initial impairment in FMD after high-intensity exercise precedes an increase in macrovascular function and that this improvement is present at least 2 h later. Thus, exercise that elicits a greater acute challenge on the vasculature may be associated with larger increases in FMD in adolescents, and the evidence of a biphasic response in FMD after high-intensity exercise is compelling.
Our failure to observe any changes in FMD immediately after MIE is consistent with the data provided by Mills et al. (22) after “low-intensity” exergaming (22); however, we extended their findings and report that endothelial function remained unchanged during the 2 h that followed. Interestingly, the lack of change in FMD in the hours after MIE is consistent with some (3,183,18), but not all (16,3916,39), data in healthy adults. However, in addition to differences in exercise stimulus, the timing of the FMD measurement and interpretation of the ratio-scaled FMD statistic (1,121,12), an independent effect of training status (16), has been observed on the acute FMD response. Furthermore, evidence suggests that age might modulate vascular reactivity to the FMD protocol (34). Although we were unable to confirm a potential confounding effect of age, maturity (Tanner stage), or aerobic fitness on the change in FMD after MIE and HIIE, it seems that a direct comparison between our findings with apparently healthy adolescents and the available adult literature may be problematic.
Shear (when expressed as SRAUC) is thought to be the main stimulus underlying the FMD response in healthy adults at rest (26). However, the relation between SRAUC and FMD is not as robust after exercise (20). Indeed, we report here that FMD remained elevated in the hours after HIIE despite a steady decline in SRAUC. The relation between SRAUC and FMD has been shown to be weak in young people even at rest (34), a finding also observed in this study. It is therefore not surprising that differences in the FMD response 1 and 2 h after exercise were independent of changes in SRAUC. Considering that baseline arterial diameter remained unchanged 1 and 2 h after MIE and HIIE and that we followed recent statistical guidelines designed to partition out the influence of vessel caliber (1), our findings are also not explained by this factor. We are therefore unable to identify the mechanism(s) underlying the disparity in FMD response presented here. It has been speculated elsewhere that the initial impairment in FMD immediately after exercise relates to an increase in oxidative stress (12,1812,18), which may reduce the bioavailability of nitric oxide (6). Although we did not measure this outcome, an increase in oxidative stress after high-intensity exercise is not consistent with the augmented FMD response observed 1 and 2 h after HIIE. Conversely, an exercise-intensity dependent increase in total antioxidant status has been reported during the hours after work-matched HIIE but not MIE (39), which would prevent the reduction in nitric oxide bioavailability associated with an increase in exercise-induced oxidative stress. However, this is not a consistent finding (16,1816,18), and we have previously reported that changes in FMD 1 h after identical HIIE in adolescents were not related to total antioxidant status (4). Alternatively, given that the exercise bouts were work-matched in the present study, our data may be explained by a positive association between the intensity of exercise and subsequent activity of endothelial nitric oxide synthase. Indeed, data in adults demonstrate that brachial artery shear increases with the intensity of cycling exercise (35), and this has been demonstrated to play a leading role in the postexercise FMD response (36). We did not quantify brachial artery shear during the exercise bouts because this is technically challenging during HIIE. However, we have previously observed a reduction in postprandial systolic blood pressure in the 5 h after HIIE, but not MIE, in adolescents (5), which would be consistent with an upregulation in endothelial nitric oxide synthase activity.
An interesting finding of the present study is that the magnitude of the increase in FMD observed 1 h after HIIE was also present after 2 h. Further study is needed to identify the precise decay in this favorable response after high-intensity exercise, although this benefit has been reported the following day in adults (39). In addition, we have previously observed that a similar increase in FMD is present 4 h after exercise despite the consumption of a meal, which impaired FMD in a nonexercise control trial (4), whereas Sedgwick et al. reported an increase in postprandial FMD the day after repeated sprint cycling in adolescent boys (30). Therefore, a single bout of HIIE seems to provide a potent stimulus for macrovascular health and may provide superior health benefits compared with MIE if repeated on a regular basis. Indeed, high-intensity interval training has been demonstrated to be more effectual in promoting macrovascular function than moderate-intensity training in adults at risk of vascular dysfunction (37) and offer superior improvements in FMD than a multidisciplinary approach in overweight adolescents (38). Furthermore, only time spent performing vigorous-intensity, but not moderate-intensity, exercise is related to vascular function in children (17).
A novel feature of this investigation was the simultaneous assessment of postocclusive reactive hyperemia in the cutaneous circulation (11) during the FMD protocol. We have demonstrated that microvascular function is improved after both MIE and HIIE and that the magnitude of this improvement is greater after HIIE. Furthermore, PRH and the total hyperemic response to occlusion remained elevated 2 h after exercise.
Our data show that transient improvements in microvascular function are possible after exercise without concomitant changes in FMD. No association has been demonstrated between FMD and reactive microvascular hyperemia in adults after exercise (31), presumably because the postocclusive cutaneous response is not mediated by nitric oxide (42). Our finding that microvascular, but not macrovascular, function was improved in the hours after MIE is probably testament to the different mechanisms underlying the postocclusive hyperemic response in our investigation, i.e., only the latter is NO mediated (42). Furthermore, the microvascular post-occlusive response may include both endothelial-independent and dependent pathways (11). It is therefore likely inappropriate to adopt measures of macrovascular health as an indication of global vascular function, especially as the earliest changes in vascular function due to the metabolic syndrome may be specifically linked to the capillary and arteriole beds, rather than the larger, conduit arteries (25). As a result, simultaneously assessing microvascular function alongside FMD may offer a novel insight regarding the effects of exercise intensity on vascular health.
We are the first to show that a single bout of MIE or HIIE can improve microvascular function in the hours after exercise and that HIIE may provide a superior benefit. Although we were unable to identify the time course of the decay in these favorable responses after exercise, Gill et al. reported that endothelium-dependent microvascular function remained elevated 16–18 h after 90 min of walking at 50% V˙O2max in adults (14). Therefore, repeating a single bout of exercise may have some utility in promoting microvascular function the following day, although this needs to be confirmed in adolescents. Conversely, there is evidence suggesting that the intensity of habitual physical activity may not influence microvascular endothelial function in adolescents (27). However, this study determined microvascular function by means that are considered to be NO dependent, which is mechanistically disparate from our assessment (42). Currently, no study has identified the efficacy of HIIE training on microvascular health in asymptomatic adolescents. Further study is therefore needed to identify whether the acute benefits in microvascular function observed in the present study translate into meaningful benefits in this group with time.
This is the first study to isolate the effect of exercise intensity on vascular function in adolescents. The strengths of this investigation include a work-matched design, control of previous physical activity and dietary factors, serial measures of macro- and microvascular function, and allometric scaling of the FMD statistic. However, apart from reporting SRAUC and baseline arterial diameter, we are not able to provide any mechanistic data that could potentially explain the changes in vascular function after MIE and HIIE. A further limitation is that we were unable to measure the time course of these changes beyond 2 h after exercise. Thus, the rate of decay in microvascular function after MIE and HIIE and macrovascular function after HIIE remains unknown. We also cannot rule out that an increase in skin temperature after exercise influenced our measure of microvascular function. However, this unavoidable confounding effect is likely limited to the time point immediately after exercise, as participants were acclimatized to the temperature-controlled (24°C) room for all other vascular measures. Furthermore, our analysis of the postocclusive reactive hyperemic response accommodates differences in baseline perfusion (42). Finally, we are unable to comment on the interaction between exercise intensity and diurnal variation in FMD. Data in adults suggest that FMD could decline by approximately 1% from baseline values over the course of our measurement period (28). However, the magnitude of this effect is far lower, and in the opposite direction, than the change observed after HIIE in the present study.
Our data indicate that the intensity of exercise has an independent effect on macro- and microvascular functions in adolescents. Specifically, macrovascular function was improved in the hours after HIIE but not after MIE. In addition, both exercise bouts promoted microvascular function, although the magnitude of this increase was greater after HIIE. Therefore, it is likely that repeating high-intensity exercises may provide superior health benefits and lower CVD risk compared with moderate-intensity activities. Given that HIIE was deemed to be more enjoyable than MIE, HIIE may provide an attractive alternative to traditional MIE.
We thank Professor Alan Batterham for assistance with the allometric scaling of the FMD data. We are also grateful to the staff and participants at Exmouth Community College (Devon, United Kingdom) for their participation in this project.
This project was funded by the Physiological Society.
The authors have no conflicts of interest to disclose. The results of the present study do not constitute endorsement by the American College of Sports Medicine.
1. Atkinson G, Batterham AM. Allometric scaling of diameter change in the original flow-mediated dilation protocol. Atherosclerosis
. 2013; 226 (2): 425–7.
2. Barker AR, Williams CA, Jones AM, Armstrong N. Establishing maximal oxygen uptake in young people during a ramp cycle test to exhaustion. Br J Sports Med
. 2011; 45 (6): 498–503.
3. Birk GK, Dawson EA, Batterham AM, et al. Effects of exercise intensity on flow mediated dilation in healthy humans. Int J Sports Med
. 2013; 34 (5): 409–14.
4. Bond B, Gates PE, Jackman S, Corless L, Williams CA, Barker AR. Exercise intensity and the protection from postprandial vascular dysfunction in adolescents. Am J Physiol Heart Circ Physiol
. 2015; 308 (11): H1443–50.
5. Bond B, Williams CA, Isic C, et al. Exercise intensity and postprandial health outcomes in adolescents. Eur J Appl Physiol
. 2015; 115 (5): 927–36.
6. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res
. 2000; 87 (10): 840–4.
7. Carson V, Rinaldi RL, Torrance B, et al. Vigorous physical activity and longitudinal associations with cardiometabolic risk factors in youth
. Int J Obes (Lond)
. 2014; 38 (1): 16–21.
8. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet
. 1992; 340 (8828): 1111–5.
9. Cohen J. Statistical Power Analysis for the Behavioural Sciences
. Hillsdale (MI): Lawrence Erlbaum; 1988.
10. Corretti MC, Anderson TJ, Benjamin EJ, et al. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol
. 2002; 39 (2): 257–65.
11. Cracowski JL, Minson CT, Salvat-Melis M, Halliwill JR. Methodological issues in the assessment of skin microvascular endothelial function
in humans. Trends Pharmacol Sciences
. 2006; 27 (9): 503–8.
12. Dawson EA, Green DJ, Cable NT, Thijssen DH. Effects of acute exercise on flow-mediated dilatation in healthy humans. J Appl Physiol (1985)
. 2013; 115 (11): 1589–98.
13. Evenson KR, Catellier DJ, Gill K, Ondrak KS, McMurray RG. Calibration of two objective measures of physical activity for children. J Sports Sci
. 2008; 26 (14): 1557–65.
14. Gill JM, Al-Mamari A, Ferrell WR, et al. Effects of prior moderate exercise on postprandial metabolism and vascular function in lean and centrally obese men. J Am Coll Cardiol
. 2004; 44 (12): 2375–82.
15. Harris RA, Nishiyama SK, Wray DW, Richardson RS. Ultrasound assessment of flow-mediated dilation. Hypertension
. 2010; 55 (5): 1075–85.
16. Harris RA, Padilla J, Hanlon KP, Rink LD, Wallace JP. The flow-mediated dilation response to acute exercise in overweight active and inactive men. Obesity (Silver Spring)
. 2008; 16 (3): 578–84.
17. Hopkins ND, Stratton G, Tinken TM, et al. Seasonal reduction in physical activity and flow-mediated dilation in children. Med Sci Sports Exerc
. 2011; 43 (2): 232–8.
18. Johnson BD, Padilla J, Wallace JP. The exercise dose affects oxidative stress and brachial artery flow-mediated dilation in trained men. Eur J Appl Physiol
. 2012; 112 (1): 33–42.
19. Khan F, Green FC, Forsyth JS, Greene SA, Morris AD, Belch JJ. Impaired microvascular function in normal children: effects of adiposity and poor glucose handling. J Physiol
. 2003; 551 (Pt 2): 705–11.
20. Llewellyn TL, Chaffin ME, Berg KE, Meendering JR. The relationship between shear rate and flow-mediated dilation is altered by acute exercise. Acta Physiol (Oxf)
. 2012; 205 (3): 394–402.
21. Mancini GB, Yeoh E, Abbott D, Chan S. Validation of an automated method for assessing brachial artery endothelial dysfunction. Can J Cardiol
. 2002; 18 (3): 259–62.
22. Mills A, Rosenberg M, Stratton G, et al. The effect of exergaming on vascular function in children. J Pediatr
. 2013; 163 (3): 806–10.
23. Motl RW, Dishman RK, Saunders R, Dowda M, Felton G, Pate RR. Measuring enjoyment of physical activity in adolescent girls. Am J Prev Med
. 2001; 21 (2): 110–7.
24. Norton K, Norton L, Sadgrove D. Position statement on physical activity and exercise intensity terminology. J Sci Med Sport
. 2010; 13 (5): 496–502.
25. Pinkney JH, Stehouwer CD, Coppack SW, Yudkin JS. Endothelial dysfunction: cause of the insulin resistance syndrome. Diabetes
. 1997; 46 (2 Suppl): S9–13.
26. Pyke KE, Tschakovsky ME. Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation? J Appl Physiol
. 2007; 102 (4): 1510–9.
27. Radtke T, Kriemler S, Eser P, Saner H, Wilhelm M. Physical activity intensity and surrogate markers for cardiovascular health in adolescents. Eur J Appl Physiol
. 2013; 113 (5): 1213–22.
28. Ringqvist A, Caidahl K, Petersson AS, Wennmalm A. Diurnal variation of flow-mediated vasodilation in healthy premenopausal women. Am J Physiol Heart Circ Physiol
. 2000; 279 (6): H2720–5.
29. Roche DM, Rowland TW, Garrard M, Marwood S, Unnithan VB. Skin microvascular reactivity in trained adolescents. Eur J Appl Physiol
. 2010; 108 (6): 1201–8.
30. Sedgwick MJ, Morris JG, Nevill ME, Barrett LA. Effect of repeated sprints on postprandial endothelial function
and triacylglycerol concentrations in adolescent boys. J Sports Sci
. 2014; 33 (8): 806–16.
31. Shamim-Uzzaman QA, Pfenninger D, Kehrer C, et al. Altered cutaneous microvascular responses to reactive hyperaemia in coronary artery disease: a comparative study with conduit vessel responses. Clin Sci (Lond)
. 2002; 103 (3): 267–73.
32. Stary HC. Evolution and progression of atherosclerotic lesions in coronary arteries of children and young adults. Arteriosclerosis
. 1989; 9 (1 Suppl): I19–32.
33. Thijssen DH, Black MA, Pyke KE, et al. Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol
. 2011; 300 (1): H2–12.
34. Thijssen DH, Bullens LM, van Bemmel MM, et al. Does arterial shear explain the magnitude of flow-mediated dilation?: a comparison between young and older humans. Am J Physiol Heart Circ Physiol
. 2009; 296 (1): H57–64.
35. Thijssen DH, Dawson EA, Black MA, Hopman MT, Cable NT, Green DJ. Brachial artery blood flow responses to different modalities of lower limb exercise. Med Sci Sports Exerc
. 2009; 41 (5): 1072–9.
36. Tinken TM, Thijssen DH, Hopkins N, et al. Impact of shear rate modulation on vascular function in humans. Hypertension
. 2009; 54 (2): 278–85.
37. Tjonna AE, Lee SJ, Rognmo O, et al. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: a pilot study. Circulation
. 2008; 118 (4): 346–54.
38. Tjonna AE, Stolen TO, Bye A, et al. Aerobic interval training reduces cardiovascular risk factors more than a multitreatment approach in overweight adolescents. Clin Sci (Lond)
. 2009; 116 (4): 317–26.
39. Tyldum GA, Schjerve IE, Tjonna AE, et al. Endothelial dysfunction induced by post-prandial lipemia: complete protection afforded by high-intensity aerobic interval exercise. J Am Coll Cardiol
. 2009; 53 (2): 200–6.
40. Vogel RA, Corretti MC, Plotnick GD. Effect of a single high-fat meal on endothelial function
in healthy subjects. Am J Cardiol
. 1997; 79 (3): 350–4.
41. Watts K, Beye P, Siafarikas A, et al. Exercise training normalizes vascular dysfunction and improves central adiposity in obese adolescents. J Am Coll Cardiol
. 2004; 43 (10): 1823–7.
42. Wong BJ, Wilkins BW, Holowatz LA, Minson CT. Nitric oxide synthase inhibition does not alter the reactive hyperemic response in the cutaneous circulation. J Appl Physiol
. 2003; 95 (2): 504–10.
43. Yelling M, Lamb K, Swaine I. Validity of a pictorial perceived exertion scale for effort estimation and effort production during stepping exercise in adolescent children. Eur Phys Educ Rev
. 2002; 8 (2): 157–75.
44. Zeiher AM, Drexler H, Wollschlager H, Just H. Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation
. 1991; 83 (2): 391–401.
Keywords:© 2015 American College of Sports Medicine
CARDIOVASCULAR DISEASE; ENDOTHELIAL FUNCTION; YOUTH; TIME COURSE