Brief Review

Antiaging Effects of Aerobic Exercise on Systemic Arteries

Hirofumi Tanaka

Whoever is always seated and does no physical age-related increase in the stiffness of central arteries leads to
exercise -even if he eats only healthy food and follows several pathological states common to older adults including
medical advice- will always be sickly and weak congestive heart failure, isolated systolic hypertension, and
—Maimonidedes, medieval Jewish philosopher orthostatic and postprandial hypotension13,14 (Figure 1). Age-
related increases in arterial stiffness do not seem to be de-

C ardiovascular disease (CVD) is the number 1 cause of

deaths in the United States and most industrialized coun-
tries. The incidence of CVD increases markedly with advanc-
pendent on the presence of clinical atherosclerotic disease. The
stiffening of arteries with advancing age has been observed in
a Chinese population in whom the prevalence of atheroscle-
ing age. In fact, age is the strongest predictor of cardiovascular rosis is low,7,15 as well as in rigorously screened US men and
risk in most risk estimates. Symptomatic clinical cardiovas- women.6,9,10 Another consequence of large artery stiffening
cular events are preceded by vascular dysfunction years or is the increased propagation of undampened or uncushioned
decades earlier. It has been well established that higher levels pressure waves to the microcirculation of low-resistance high-
of regular physical activity are associated with reduced cardi- flow organs such as the brain and kidneys16 (Figure 1).
ovascular events and mortality.1 Accordingly, increasing levels The present brief review focuses on the influence of reg-
of physical activity are the first-line approaches for prevent- ular exercise on arterial stiffness—one of the key macrovascu-
ing and treating vascular dysfunction and cardiometabolic lar functions. Regular exercise elicits a variety of adaptations
diseases. The precise mechanisms underlying the beneficial in microvascular functions. For more details, readers are re-
effects of physical activity are unclear but have been attributed ferred to previous reviews on this topic.17,18
to improvements in traditional CVD risk factors such as blood
pressure, plasma lipoproteins, and obesity. However, the con- Cross-Sectional Studies on Aerobic Exercise
tribution of these various risk factors to the physical activity– Since chronic or lifelong effects of habitual exercise are dif-
related risk reduction in coronary heart disease and CVD is ficult to conduct, cross-sectional approaches have been fre-
surprisingly small with only 35% to 60% can be explained by a
Downloaded from http://ahajournals.org by on October 5, 2020

quently used to address the influence of habitual exercise on

comprehensive list of 7 traditional risk factors.2 One of the rea- aging vasculature (Figure 2, blue arrows). Cross-sectional
sons may be that none of these traditional risk factors measure comparisons indicate that middle-aged and older adults who
functions of the vasculature that play important roles in patho- performed endurance training on a regular basis demonstrate
physiology and pathogenesis of CVD. a higher central arterial compliance (lower arterial stiffness)
As illustrated in the Thomas Sydenham axiom that “man compared with age-matched sedentary peers.6,9,10 In a large
is as old as his arteries,” arterial health, more specifically ar- population-based sample of community-dwelling older adults,
terial stiffness/compliance, has been widely regarded as a ba- higher physical activity in late life is associated with lower ar-
rometer of biological or physiological aging. The mechanisms terial stiffness and pressure pulsatility.4 More importantly, the
underlying the protective effects of regular physical activity associations were stronger when the analyses were restricted
on CVD may likely include enhanced arterial compliance or to participants with persistent levels of physical activity from
reduced arterial stiffness.3,4 Arterial stiffness reflects the ability mid-to-late life.4 These results obtained in US communities
of central elastic arteries (eg, aorta and carotid artery) to ex- are consistent with a European community–based study show-
pand and recoil with cardiac pulsation and relaxation.5 During ing the moderate-to-vigorous physical activity was associated
systole, a significant portion of the ejected stroke volume is with a slower age-related progression of central arterial stiff-
stored by arterial distention, which acts to buffer the rise in ness.19 Taken together, these cross-sectional findings suggest
systolic pressure and maintain a continuous blood flow in the that habitual physical activity is an effective strategy for the
capillary beds. primary prevention of arterial stiffening that occurs with
In sedentary humans, arterial stiffness in the central (car- advancing age.
diothoracic) circulation increases with advancing age even in
healthy men and women.6–10 Elevations in arterial stiffness are Interventional Studies on Aerobic Exercise
believed to contribute significantly to the pathophysiology Daily brisk walking for ≈3 months improves carotid ar-
of the age-related increase in CVD and, accordingly, have tery compliance in previously sedentary but healthy mid-
been identified as an independent risk factor.5,11,12 Indeed, an dle-aged and older men,10 as well as in apparently healthy

From the Cardiovascular Aging Research Laboratory, Department of Kinesiology and Health Education, The University of Texas at Austin.
Correspondence to Hirofumi Tanaka, Department of Kinesiology and Health Education, The University of Texas at Austin, 2109 San Jacinto Blvd,
D3700 Austin, TX 78712. Email [email protected]
(Hypertension. 2019;74:237-243. DOI: 10.1161/HYPERTENSIONAHA.119.13179.)
© 2019 American Heart Association, Inc.
Hypertension is available at https://www.ahajournals.org/journal/hyp DOI: 10.1161/HYPERTENSIONAHA.119.13179

237
 238  Hypertension   August 2019

Figure 1.  A myriad of physiological, functional,

and clinical sequela of arterial stiffening that
occurs with increasing age.

postmenopausal women20 to levels seen in age-matched stiffness has been reported in patients with hypertension and
endurance-trained adults (Figure 2, red arrow). The ability of diabetes mellitus.22–24 The appropriate prescription of exercise
Downloaded from http://ahajournals.org by on October 5, 2020

regular aerobic exercise to reduce arterial stiffness in this pop- as a preventive and treatment strategy should include a choice
ulation does not depend on changes in body weight, arterial of the suitable modality of exercise. In the pharmacological
blood pressure, risk factors for coronary artery disease, or car- treatment of hypertension, it is a standard practice to change
diovascular fitness.10 More importantly, these effects can be the class of antihypertensive medications if one drug is found
accomplished with an intensity (moderate) and type (walking) to be ineffective. In the exercise prescription, however, it is not
of physical activity that can be performed by most, if not all, a common practice to change the mode of exercise when one
healthy adults.10,20 The destiffening effects of aerobic exercise mode of exercise fails to improve. Could swimming exercise
have been observed in other modes of aerobic exercises in- performed in the water be effective as a destiffening therapy
cluding cycling.21 for aging vasculature in patient populations? Swimming exer-
In contrast to the findings in apparently healthy aging cise intervention was demonstrated to be effective in reducing
adults, the efficacy of regular walking exercise remains con- central artery stiffness in middle-aged and older adults with
troversial in patient populations as a lack of effects on arterial essential hypertension.25,26 In contrast to the public perception

Figure 2.  Antiaging destiffening effects of

regular aerobic exercise. Cross-sectional or
observational studies indicate that sedentary
aging is associated with vascular stiffening,
whereas physically active aging is related to the
attenuation and absence of vascular stiffening
(blue arrows). Aerobic exercise intervention
studies demonstrated that aerobic exercise
interventions reduce arterial stiffness in older
adults (red arrow).
 Tanaka   Aging, Vascular Stiffness, and Exercise   239

Figure 3.  Influence of advancing age on central

artery stiffness and its underlying physiological
mechanisms. Both structural and functional
elements that have been implicated in the
vascular stiffening processes with advancing
are highlighted.

that swimming is a minor form of exercise, it is one of the altered over a much shorter period, even acutely. The ability
most popular and most practiced forms of physical activity. to modify arterial stiffness over a period of days or weeks
Swimming is an attractive form of exercise because it is is thought to be because of, at least in part, modulation of
easily accessible, inexpensive, and isotonic.27 Because of the the contractile states and intrinsic stiffening of the vascular
buoyancy of water, compressive stress on joints is low and smooth muscle cells in the arterial wall.34 The research find-
orthopedic injury rate is low.28 Because of cold temperature ing in the animal model that age-related aortic stiffening was
and increased thermoconductivity of surrounding water, heat- suppressed when actin depolymerization was applied supports
related illness is extremely low.29 Thus, swimming can be an the role of smooth muscle cells.35 Among the factors that in-
ideal modality of destiffening exercise for aging adults who fluence the contractile states of the vascular smooth muscle
tend to be obese and experience joint problems including cells, the reduction in sympathetic adrenergic vasoconstrictor
osteoarthritis.30 tone seems to play a major role in exercise-induced decrease
Downloaded from http://ahajournals.org by on October 5, 2020

in arterial stiffness.
Physiological Mechanisms Direct recording of muscle sympathetic nerve activity
Arterial stiffness is primarily determined by the intrinsic (MSNA) through microneurography is the most robust way to
elastic properties of the arterial wall. Structural changes in measure sympathetic nerve activity in humans. MSNA inner-
the arterial wall, particularly decreased density of elastin with vating vascular smooth muscle cells in various skeletal muscle
corresponding increases in collagen content, are thought to tissues is similar,36 and the data from animal experiments in-
play a major role in age-associated increases in central arterial dicate that cervical (neck) sympathetic nerve activities pos-
stiffness (Figure 3). However, the elastin-collagen composi- itively correlate with lumbar sympathetic nerve activities
tion of the arterial wall represents a more chronic component directed to the leg muscle vasculature.37 There is a signifi-
of the arterial stiffness. It is unlikely that this may be a physi- cant and inverse relation between carotid artery stiffness and
ological mechanism underlying reductions in arterial stiffness MSNA in healthy men varying widely in age.38 A recent study
induced by short-term aerobic exercise interventions. In fact, demonstrated that elevated MSNA contributes to central ar-
an animal experiment has demonstrated that the influence of tery stiffness in humans.39
regular exercise on arterial stiffness does not seem to be medi- Aerobic exercise training reduces resting MSNA in mid-
ated by the quantitative changes in arterial wall elastin and dle-aged and older adults.40 In a study involving middle-aged
collagen.31 Another animal study using the DNA microarray and older adults, arterial stiffness decreased significantly with
technique showed that exercise training was not related to al- systemic α-adrenergic blockade phentolamine before the ex-
tered expressions in genes associated with structural proteins ercise training intervention, suggesting a substantial chronic
(eg, various types of collagens and procollagens) or enzymes restraint placed on the elastic artery by the sympathetic vas-
that modulate these proteins (eg, collagenase and matrix cular tone.41 After the exercise training, however, arterial
metalloproteinase).32 However, a previous study using wheel stiffness was not affected by α-adrenergic blockade.41 These
running in mice reported a small influence of regular exercise results indicate that sympathetic adrenergic vasoconstrictor
on total collagen content in the carotid artery but significant tone acting on the vasculature was removed with regular aer-
reductions in collagen I and III density.33 As such, qualita- obic exercise. Endothelin-1 is the most potent endothelium-
tive, rather than quantitative, changes in arterial wall collagen derived vasoconstrictor peptide and could play a role in
may contribute to the destiffening effects of regular aerobic mediating the habitual aerobic exercise–induced decrease in
exercise. central arterial stiffness. Carotid artery stiffness decreased
In contrast to the prevailing thought that arterial stiff- with the administration of the endothelin receptor blockade
ness is a relatively static measure that requires years of time before exercise intervention.42 After exercise training, how-
to change, arterial stiffness has a large reserve and can be ever, decreases in carotid artery stiffness previously observed
 240  Hypertension   August 2019

with the endothelin receptor blockade before training were overall exercise and fitness programs if it was shown to have
abolished.42 These results suggest that the vasoconstrictor positive effects on cardiovascular functions in general and ar-
tone affecting central elastic arteries decreased with endur- terial stiffness in particular.
ance training, thereby removing a tonic restraint placed on the What effects does resistance exercise training exert on ar-
arterial compliance and enhancing its elasticity. terial stiffness? In the first cross-sectional study to address this
The impact of aerobic exercise training on arterial stiff- question, young men who performed resistance training on a
ness manifests more clearly in central (elastic) than peripheral regular basis demonstrated greater levels of arterial stiffness
(muscular) arteries.9,43 Because the effect of vasoconstrictor than their sedentary peers.53 In the subsequent study, strength-
tone exerted by smooth muscle cells is expected to be greater trained middle-aged men exhibited elevated levels of arterial
in more peripheral arteries by virtue of greater smooth muscle stiffness, and the age-related increase in arterial stiffness was
cells, it may argue against the possibility that reduced vaso- greater in the resistance-trained men than in sedentary con-
constrictor tone would be a mechanism underlying the effect trols.54 Given the well-known limitation of cross-sectional
of exercise training on the stiffness of central elastic arteries. study design and the conflicting results between aerobic and
However, it is plausible to hypothesize that mechanical fac- resistance training, intervention studies were required to at-
tors may have interacted with functional elements to modu- tribute the observed group differences to the resistance train-
late arterial stiffness since beat-by-beat arterial distension is ing per se.
substantially greater in central versus peripheral arteries. This In the first exercise intervention study to address this, a few
viscous property of the arterial wall is the basis for the heart months of resistance training significantly increased arterial
rate dependence of arterial stiffness in vivo as the effect of stiffness in healthy men.55 If the changes in arterial stiffness
heart rate is much greater in elastic than in muscular arter- were mediated by resistance training, such changes should re-
ies.44 Indeed, vascular smooth muscle cells are implicated to turn to the baseline level when the stimuli of daily resistance
be major regulatory factors of arterial stiffness.45 In animal exercise were removed. During the detraining period, arterial
models, the activation of smooth muscle contraction produces stiffness, which was increased with resistance training, was
≈10% reduction in carotid artery diameter.46 Aortas from reversed to the baseline values.55 The arterial stiffening effects
smooth muscle knockout mice demonstrate severe degrada- of strenuous resistance training have also been observed in
tion of elastin and elastic lamellae and the resultant arterial young women56 and have been confirmed by other interven-
stiffening.47 Vascular smooth muscle cells have been impli- tion studies.57–59
cated in the recruitment of both elastin and collagen during It is not clear how strenuous resistance training exerts
the contractile responses.45 vascular stiffening effects in young and middle-aged adults.
Downloaded from http://ahajournals.org by on October 5, 2020

Endurance-trained middle-aged and older adults demon- During each bout of resistance exercise, arterial blood pres-
strate greater endothelium-dependent vasodilation than their sure is known to increase to as high as ≈320/250 mm Hg.60
sedentary peers, and previously sedentary middle-aged and These acute intermittent elevations in arterial blood pressure
older adults show improved endothelial function after aerobic during resistance exercise may have altered the arterial struc-
exercise intervention.17,48 Considering that NO bioavailability ture and the arterial load–bearing properties of collagen and
is an important regulatory mechanism of vasomotor tone, it elastin, thereby causing arterial stiffening. Indeed, arterial
is plausible to hypothesize that the endothelial function may stiffening in resistance-trained adults is associated with the
play a role in the destiffening effects of aerobic exercise. From thickening of the arterial wall.54 If chronic resistance train-
the experimental standpoint, it is ideal to locally manipulate ing does in fact exacerbate the age-related increase in arterial
factors influencing vasoconstrictor states. However, such ma- stiffness, then resistance exercise prescription to combat sar-
nipulation is difficult to conduct when the experimental target copenia, osteopenia, and glucose intolerance may need to be
is central arteries (eg, aorta and carotid artery). The available revisited and modified. It should be noted that these vascular
evidence using systemic infusion of NO blockers remains stiffening effects of resistance training have not been observed
highly controversial.49,50 In an aerobic exercise intervention in older adults with already elevated arterial stiffness as long
study involving middle-aged and older adults, baseline arte- as a resistance exercise program was consistent with the rec-
rial stiffness was reduced with exercise training. However, ommended guidelines established by the American Heart
changes in arterial stiffness induced by NO synthase blocker Association.61–64
were not different before and after exercise training.41 Yoga can be considered a series of whole-body isometric
contractions associated with yoga postures. It also contains
Effects of Resistance Training various elements that could potentially influence vascular
As illustrated by the physical appearance of old endurance functions, including meditation and stretching.61,65 However,
runners, regular aerobic exercise exerts limited impact on the available studies in middle-aged and older adults did not
enhancing muscle mass and strength. Indeed, an age-related observe arterial destiffening effects after hatha yoga66 or hot
loss in muscle strength in older adults who perform chronic (Bikram) yoga.67
endurance training alone is no different from that of their
sedentary peers.51,52 Accordingly, contemporary statements Effects of Cross-Training
on physical activity by various health organizations have rec- One of the most effective ways to maximize benefits from both
ommended resistance training as an essential part of physical aerobic exercise and resistance exercise seems to be the con-
activity preventive and rehabilitative programs. Resistance current performance of both training (ie, cross-training).68,69
training could become an even more essential component of Theoretically, the opposing effects of aerobic and strength
 Tanaka   Aging, Vascular Stiffness, and Exercise   241

training exercise on central artery stiffness should negate the to reduce blood pressure in spontaneous hypertensive rats,
adverse effects of resistance training if aerobic exercise train- and its antihypertensive effect is attributed to an inhibition
ing effects equals or exceeds resistance training effects. This of angiotensin-converting enzyme.74 In the human clinical in-
hybrid approach is consistent with the latest exercise guide- vestigation, regular ingestion of LTP and regular participation
lines suggesting concurrent practices of aerobic, resistance, in aerobic exercise significantly reduced carotid artery stiff-
and flexibility exercise training as the recommended approach ness in postmenopausal women. When the ingestion of LTP
to enhance both overall physical fitness and health. was superimposed on the exercise training intervention, the
Rowing exercise is an intriguing and unique model of effects on arterial stiffness were additive and synergistic as
physical exercise that includes components of both aer- the magnitude of improvement was significantly greater in the
obic endurance and muscular strength. Rowers require large combined intervention than either treatment alone.75 A similar
muscle strength for the acceleration of the boat at the race additive effect of regular exercise and LTP has been observed
start and a high endurance capacity to maintain this speed on the endothelial function as well.76 These results suggest
during the race.70 Likewise, rowers perform a combination that depending on the proper matchup, regular aerobic exer-
of endurance training and strength training during their usual cise can be combined with other lifestyle modifications (ie,
training regimen as demonstrated by their large maximal aer- dietary changes) to produce greater benefits for arterial health.
obic capacity and muscular strength.71 Central artery stiffness
is lower in habitual rowers than in age-matched sedentary Perspectives
peers who are matched for age, body mass, metabolic risk Vascular function in general and arterial stiffness in partic-
factors, blood pressure, and sodium intake.72 The results of ular is a barometer for CVD risks that increase markedly with
subsequent interventional studies are consistent with this advancing age. Arterial stiffness was thought of as a relatively
cross-sectional study. Concurrently performed endurance static measure and cannot be changed easily. In contrast to
training minimized arterial stiffening that was accompanied the once-held notion, arterial stiffness can be modified with
by high-intensity resistance training.57 In addition, there was regular aerobic exercise. As Benjamin Franklin advised as
a tendency for arterial stiffness to decrease with combined “an ounce of prevention is worth a pound of cure,” preven-
endurance and resistance training.57,73 In a study involving tion, either primary or secondary, is a key for preventing and
healthy postmenopausal women, 3 months of combined cir- treating vascular dysfunction in CVD-threatened aging adults.
cuit weight training and endurance training reduced pulse Regularly performed aerobic exercise not only acts to prevent
wave velocity, an index of arterial stiffness.73 From the vascular stiffening but also reverse vascular stiffening that
standpoint of exercise adherence and compliance, this type was induced initially by aging process. The practice of reg-
Downloaded from http://ahajournals.org by on October 5, 2020

of cross-training is highly beneficial as it is more enjoyable, ular aerobic exercise can be easily accomplished by most, if
acts to reduce overuse injuries, and breaks the boredom that not all, older adults and can be combined with other lifestyle
often results from long-term participation in a single exercise modifications. Habitual aerobic exercise should be a corner-
mode.68,69 Thus, stiffening of the large arteries can be avoided stone of such effort and a prescription for life. Exercise can be
if endurance training is incorporated into an exercise program a component of personal hygiene, and the first step in every
that has a strenuous strength training component. recipe can be physical activity. Exercise is truly medicine for
vascular health.
Exercise as a Part of the Hybrid
or Adjunct Therapy Sources of Funding
None.
Regular aerobic exercise is often the first-line approach for
the prevention and treatment of vascular dysfunctions and
Disclosures
physical impairments that are associated with advancing age. None.
In typical clinical settings, regular exercise is not prescribed
in isolation but rather with other lifestyle interventions (eg, References
dietary modifications, weight loss, and smoking cessation). 1. Kaminsky LA, Arena R, Ellingsen Ø, Harber MP, Myers J, Ozemek C,
A question of whether the influence of regular aerobic exer- Ross R. Cardiorespiratory fitness and cardiovascular disease - The
cise could be additive to the effect of other popular lifestyle past, present, and future. Prog Cardiovasc Dis. 2019;62:86–93. doi:
10.1016/j.pcad.2019.01.002
modifications (eg, sodium restriction, Mediterranean diet) 2. Mora S, Cook N, Buring JE, Ridker PM, Lee IM. Physical activity and reduced
is clearly important and should be investigated but has not risk of cardiovascular events: potential mediating mechanisms. Circulation.
been addressed widely. This is because it is difficult to tease 2007;116:2110–2118. doi: 10.1161/CIRCULATIONAHA.107.729939
3. Tanaka H, Dinenno FA, Monahan KD, DeSouza CA, Seals DR. Carotid
out the effect of one intervention from others when multiple
artery wall hypertrophy with age is related to local systolic blood pressure
lifestyle modifications were prescribed. A properly designed in healthy men. Arterioscler Thromb Vasc Biol. 2001;21:82–87.
research study would require 4 groups that include controls, 4. Tanaka H, Palta P, Folsom AR, Meyer ML, Matsushita K, Evenson KR,
exercise group, other lifestyle modification group, and com- Aguilar D, Heiss G. Habitual physical activity and central artery stiff-
ening in older adults: the Atherosclerosis Risk in Communities study. J
bination group. Hypertens. 2018;36:1889–1894. doi: 10.1097/HJH.0000000000001782
Calpis sour milk is cultured milk produced by fermented 5. Arnett DK, Evans GW, Riley WA. Arterial stiffness: a new cardiovas-
skim milk with a natural starter culture containing several cular risk factor? Am J Epidemiol. 1994;140:669–682. doi: 10.1093/
oxfordjournals.aje.a117315
microorganisms. This commercial drink has been widely con-
6. Vaitkevicius PV, Fleg JL, Engel JH, O’Connor FC, Wright JG, Lakatta LE,
sumed in Japan for many years, especially by children and is Yin FC, Lakatta EG. Effects of age and aerobic capacity on arterial stiff-
known to contain LTP (lactotripeptide). LTP has been found ness in healthy adults. Circulation. 1993;88(4 pt 1):1456–1462.
 242  Hypertension   August 2019

7. Avolio AP, Deng FQ, Li WQ, Luo YF, Huang ZD, Xing LF, O’Rourke MF. 29. Sheldahl LM, Buskirk ER, Loomis JL, Hodgson JL, Mendez J. Effects of
Effects of aging on arterial distensibility in populations with high and low exercise in cool water on body weight loss. Int J Obes. 1982;6:29–42.
prevalence of hypertension: comparison between urban and rural com- 30. Alkatan M, Baker JR, Machin DR, Park W, Akkari AS, Pasha EP,
munities in China. Circulation. 1985;71:202–210. Tanaka H. Improved function and reduced pain after swimming and cy-
8. Kelly R, Hayward C, Avolio A, O’Rourke M. Noninvasive determi- cling training in patients with osteoarthritis. J Rheumatol. 2016;43:666–
nation of age-related changes in the human arterial pulse. Circulation. 672. doi: 10.3899/jrheum.151110
1989;80:1652–1659. 31. Nosaka T, Tanaka H, Watanabe I, Sato M, Matsuda M. Influence of
9. Tanaka H, DeSouza CA, Seals DR. Absence of age-related increase in regular exercise on age-related changes in arterial elasticity: mecha-
central arterial stiffness in physically active women. Arterioscler Thromb nistic insights from wall compositions in rat aorta. Can J Appl Physiol.
Vasc Biol. 1998;18:127–132. 2003;28:204–212.
10. Tanaka H, Dinenno FA, Monahan KD, Clevenger CM, DeSouza CA, 32. Maeda S, Iemitsu M, Miyauchi T, Kuno S, Matsuda M, Tanaka H. Aortic
Seals DR. Aging, habitual exercise, and dynamic arterial compliance. stiffness and aerobic exercise: mechanistic insight from microarray analy-
Circulation. 2000;102:1270–1275. ses. Med Sci Sports Exerc. 2005;37:1710–1716.
11. Riley WA, Freedman DS, Higgs NA, Barnes RW, Zinkgraf SA,
33. Fleenor BS, Marshall KD, Durrant JR, Lesniewski LA,
Berenson GS. Decreased arterial elasticity associated with cardiovascular Seals DR. Arterial stiffening with ageing is associated with trans-
disease risk factors in the young. Bogalusa Heart Study. Arteriosclerosis. forming growth factor-β1-related changes in adventitial collagen: re-
1986;6:378–386. versal by aerobic exercise. J Physiol. 2010;588(pt 20):3971–3982. doi:
12. Hodes RJ, Lakatta EG, McNeil CT. Another modifiable risk factor for 10.1113/jphysiol.2010.194753
cardiovascular disease? Some evidence points to arterial stiffness. J Am 34. Benetos A, Huguet F, Albaladejo P, Brisac AM, Pappo M, Safar ME,
Geriatr Soc. 1995;43:581–582. Levy BI. Role of adrenergic tone in mechanical and functional properties
13. Rowe JW. Clinical consequences of age-related impairments in vascular of carotid artery during aging. Am J Physiol. 1993;265(4 pt 2):H1132–
compliance. Am J Cardiol. 1987;60:68G–71G. H1138. doi: 10.1152/ajpheart.1993.265.4.H1132
14. O’Rourke M. Arterial stiffness, systolic blood pressure, and logical treat- 35. Qiu H, Zhu Y, Sun Z, Trzeciakowski JP, Gansner M, Depre C,
ment of arterial hypertension. Hypertension. 1990;15:339–347. Resuello RR, Natividad FF, Hunter WC, Genin GM, Elson EL, Vatner DE,
15. Avolio AP, Chen SG, Wang RP, Zhang CL, Li MF, O’Rourke MF. Effects Meininger GA, Vatner SF. Short communication: vascular smooth muscle
of aging on changing arterial compliance and left ventricular load in a cell stiffness as a mechanism for increased aortic stiffness with aging. Circ
northern Chinese urban community. Circulation. 1983;68:50–58. Res. 2010;107:615–619. doi: 10.1161/CIRCRESAHA.110.221846
16. Tarumi T, Shah F, Tanaka H, Haley AP. Association between cen- 36. Ray CA, Mark AL. Sympathetic nerve activity to nonactive muscle
tral elastic artery stiffness and cerebral perfusion in deep subcortical of the exercising and nonexercising limb. Med Sci Sports Exerc.
gray and white matter. Am J Hypertens. 2011;24:1108–1113. doi: 1995;27:183–187.
10.1038/ajh.2011.101 37. Trzebski A, Baradziej S. Role of the rostral ventrolateral medulla in the
17. Green DJ, Hopman MT, Padilla J, Laughlin MH, Thijssen DH. Vascular generation of synchronized sympathetic rhythmicities in the rat. J Auton
adaptation to exercise in humans: role of hemodynamic stimuli. Physiol Nerv Syst. 1992;41:129–139.
Rev. 2017;97:495–528. doi: 10.1152/physrev.00014.2016 38. Tanaka H, Dinenno FA, Seals DR. Reductions in central arterial compli-
18. Muller-Delp JM. Heterogeneous ageing of skeletal muscle microvascular ance with age are related to sympathetic vasoconstrictor nerve activity in
function. J Physiol. 2016;594:2285–2295. doi: 10.1113/JP271005 healthy men. Hypertens Res. 2017;40:493–495. doi: 10.1038/hr.2016.182
19. Ahmadi-Abhari S, Sabia S, Shipley MJ, Kivimaki M, Singh-Manoux A, 39. Holwerda SW, Luehrs RE, Collins MT, Wooldridge NA,
Downloaded from http://ahajournals.org by on October 5, 2020

Tabak A, McEniery C, Wilkinson IB, Brunner EJ. Physical activity, Stroud AK, Fadel PJ, Abboud FM, Pierce GL. Elevated muscle sym-
sedentary behavior, and long-term changes in aortic stiffness: the pathetic nerve activity contributes to central artery stiffness in young
Whitehall II study. J Am Heart Assoc. 2017;6:e005974. doi: 10.1161/JAHA. and middle-age/older adults. Hypertension. 2019;73:1025–1035. doi:
117.005974 10.1161/HYPERTENSIONAHA.118.12462
20. Moreau KL, Donato AJ, Seals DR, DeSouza CA, Tanaka H. Regular exer- 40. Laterza MC, de Matos LD, Trombetta IC, Braga AM, Roveda F, Alves MJ,
cise, hormone replacement therapy and the age-related decline in carotid Krieger EM, Negrão CE, Rondon MU. Exercise training restores baro-
arterial compliance in healthy women. Cardiovasc Res. 2003;57:861–868. reflex sensitivity in never-treated hypertensive patients. Hypertension.
doi: 10.1016/s0008-6363(02)00777-0 2007;49:1298–1306. doi: 10.1161/HYPERTENSIONAHA.106.085548
21. Mora-Rodriguez R, Ramirez-Jimenez M, Fernandez-Elias VE, 41. Sugawara J, Komine H, Hayashi K, Yoshizawa M, Otsuki T, Shimojo N,
Guio de Prada MV, Morales-Palomo F, Pallares JG, Nelson RK, Ortega JF. Miyauchi T, Yokoi T, Maeda S, Tanaka H. Reduction in alpha-adrenergic
Effects of aerobic interval training on arterial stiffness and microvas- receptor-mediated vascular tone contributes to improved arterial com-
cular function in patients with metabolic syndrome. J Clin Hypertens pliance with endurance training. Int J Cardiol. 2009;135:346–352. doi:
(Greenwich). 2018;20:11–18. doi: 10.1111/jch.13130 10.1016/j.ijcard.2008.04.007
22. Aizawa K, Petrella RJ. Acute and chronic impact of dynamic exercise 42. Maeda S, Sugawara J, Yoshizawa M, Otsuki T, Shimojo N, Jesmin S,
on arterial stiffness in older hypertensives. Open Cardiovasc Med J. Ajisaka R, Miyauchi T, Tanaka H. Involvement of endothelin-1 in habitual
2008;2:3–8. doi: 10.2174/1874192400802010003 exercise-induced increase in arterial compliance. Acta Physiol (Oxf).
23. Ferrier KE, Waddell TK, Gatzka CD, Cameron JD, Dart AM, Kingwell BA. 2009;196:223–229. doi: 10.1111/j.1748-1716.2008.01909.x
Aerobic exercise training does not modify large-artery compliance in iso- 43. Shibata S, Fujimoto N, Hastings JL, Carrick-Ranson G, Bhella PS,
lated systolic hypertension. Hypertension. 2001;38:222–226. Hearon CM Jr, Levine BD. The effect of lifelong exercise frequency on
24. Seals DR, Tanaka H, Clevenger CM, Monahan KD, Reiling MJ, arterial stiffness. J Physiol. 2018;596:2783–2795. doi: 10.1113/JP275301
Hiatt WR, Davy KP, DeSouza CA. Blood pressure reductions with ex- 44. Mangoni AA, Mircoli L, Giannattasio C, Ferrari AU, Mancia G. Heart rate-
ercise and sodium restriction in postmenopausal women with elevated dependence of arterial distensibility in vivo. J Hypertens. 1996;14:897–901.
systolic pressure: role of arterial stiffness. J Am Coll Cardiol. 2001;38: 45. Brozovich FV, Nicholson CJ, Degen CV, Gao YZ, Aggarwal M,
506–513. Morgan KG. Mechanisms of vascular smooth muscle contraction and the
25. Nualnim N, Parkhurst K, Dhindsa M, Tarumi T, Vavrek J, Tanaka H. basis for pharmacologic treatment of smooth muscle disorders. Pharmacol
Effects of swimming training on blood pressure and vascular function Rev. 2016;68:476–532. doi: 10.1124/pr.115.010652
in adults >50 years of age. Am J Cardiol. 2012;109:1005–1010. doi: 46. Hudetz AG, Márk G, Kovách AG, Monos E. The effect of smooth muscle
10.1016/j.amjcard.2011.11.029 activation on the mechanical properties of pig carotid arteries. Acta
26. Wong A, Kwak YS, Scott SD, Pekas EJ, Son WM, Kim JS, Park SY. The Physiol Acad Sci Hung. 1980;56:263–273.
effects of swimming training on arterial function, muscular strength, and 47. Fry JL, Shiraishi Y, Turcotte R, Yu X, Gao YZ, Akiki R, Bachschmid M,
cardiorespiratory capacity in postmenopausal women with stage 2 hyper- Zhang Y, Morgan KG, Cohen RA, Seta F. Vascular smooth muscle sirtuin-1
tension. Menopause. 2018;26:653–658. protects against aortic dissection during angiotensin II-Induced hyperten-
27. Tanaka H. Swimming exercise: impact of aquatic exercise on sion. J Am Heart Assoc. 2015;4:e002384. doi: 10.1161/JAHA.115.002384
cardiovascular health. Sports Med. 2009;39:377–387. doi: 10.2165/ 48. Seals DR, Desouza CA, Donato AJ, Tanaka H. Habitual exercise
00007256-200939050-00004 and arterial aging. J Appl Physiol (1985). 2008;105:1323–1332. doi:
28. Levy CM, Kolin E, Berson BL. Cross training: risk or benefit? an eval- 10.1152/japplphysiol.90553.2008
uation of injuries in four athlete populations. Sports Med Clin Forum. 49. Sugawara J, Saito Y, Maeda S, Yoshizawa M, Komine H, Nakamura M,
1986;3:1–8. Ajisaka R, Tanaka H. Lack of changes in carotid artery compliance with
 Tanaka   Aging, Vascular Stiffness, and Exercise   243

systemic nitric oxide synthase inhibition. J Hum Hypertens. 2014;28:494– reactivity in normotensive postmenopausal women. Eur J Appl Physiol.
499. doi: 10.1038/jhh.2013.137 2007;100:403–408. doi: 10.1007/s00421-007-0447-2
50. Stewart AD, Millasseau SC, Kearney MT, Ritter JM, Chowienczyk PJ. 64. Jefferson ME, Nicklas BJ, Chmelo EA, Crotts CI, Shaltout HA, Diz DI,
Effects of inhibition of basal nitric oxide synthesis on carotid-femoral Marsh AP, Brinkley TE. Effects of resistance training with and without ca-
pulse wave velocity and augmentation index in humans. Hypertension. loric restriction on arterial stiffness in overweight and obese older adults.
2003;42:915–918. doi: 10.1161/01.HYP.0000092882.65699.19 Am J Hypertens. 2016;29:494–500. doi: 10.1093/ajh/hpv139
51. Tarpenning KM, Hawkins SA, Marcell TJ, Wiswell RA. Endurance exer- 65. Yamamoto K, Kawano H, Gando Y, Iemitsu M, Murakami H, Sanada K,
cise and leg strength in older women. J Aging Phys Act. 2006;14:3–11. Tanimoto M, Ohmori Y, Higuchi M, Tabata I, Miyachi M. Poor trunk
52. Marcell TJ, Hawkins SA, Wiswell RA. Leg strength declines with advanc- flexibility is associated with arterial stiffening. Am J Physiol Heart Circ
ing age despite habitual endurance exercise in active older adults. J Strength Physiol. 2009;297:H1314–H1318. doi: 10.1152/ajpheart.00061.2009
Cond Res. 2014;28:504–513. doi: 10.1519/JSC.0b013e3182a952cc 66. Hunter SD, Tarumi T, Dhindsa MS, Nualnim N, Tanaka H. Hatha yoga and
53. Bertovic DA, Waddell TK, Gatzka CD, Cameron JD, Dart AM, vascular function: results from cross-sectional and interventional studies. J
Kingwell BA. Muscular strength training is associated with low arterial Bodyw Mov Ther. 2013;17:322–327. doi: 10.1016/j.jbmt.2012.10.009
compliance and high pulse pressure. Hypertension. 1999;33:1385–1391. 67. Hunter SD, Dhindsa MS, Cunningham E, Tarumi T, Alkatan M,
54. Miyachi M, Donato AJ, Yamamoto K, Takahashi K, Gates PE, Nualnim N, Tanaka H. The effect of Bikram yoga on arterial stiffness in
Moreau KL, Tanaka H. Greater age-related reductions in central arterial young and older adults. J Altern Complement Med. 2013;19:930–934. doi:
compliance in resistance-trained men. Hypertension. 2003;41:130–135. 10.1089/acm.2012.0709
55. Miyachi M, Kawano H, Sugawara J, Takahashi K, Hayashi K, Yamazaki 68. Tanaka H, Swensen T. Impact of resistance training on endurance perfor-
K, Tabata I, Tanaka H. Unfavorable effects of resistance training on cen- mance. A new form of cross-training? Sports Med. 1998;25:191–200. doi:
tral arterial compliance: a randomized intervention study. Circulation. 10.2165/00007256-199825030-00005
2004;110:2858–2863. doi: 10.1161/01.CIR.0000146380.08401.99 69. Tanaka H. Effects of cross-training. Transfer of training effects on VO2max
56. Cortez-Cooper MY, DeVan AE, Anton MM, Farrar RP, Beckwith KA, between cycling, running and swimming. Sports Med. 1994;18:330–339.
Todd JS, Tanaka H. Effects of high intensity resistance training on arterial doi: 10.2165/00007256-199418050-00005
stiffness and wave reflection in women. Am J Hypertens. 2005;18:930– 70. Steinacker JM. Physiological aspects of training in rowing. Int J Sports
934. doi: 10.1016/j.amjhyper.2005.01.008 Med. 1993;14(suppl 1):S3–S10.
57. Kawano H, Tanaka H, Miyachi M. Resistance training and arterial compli- 71. Secher NH. Physiological and biomechanical aspects of rowing.
ance: keeping the benefits while minimizing the stiffening. J Hypertens. Implications for training. Sports Med. 1993;15:24–42. doi: 10.2165/
2006;24:1753–1759. doi: 10.1097/01.hjh.0000242399.60838.14 00007256-199315010-00004
58. Okamoto T, Masuhara M, Ikuta K. Upper but not lower limb resist- 72. Cook JN, DeVan AE, Schleifer JL, Anton MM, Cortez-Cooper MY,
ance training increases arterial stiffness in humans. Eur J Appl Physiol. Tanaka H. Arterial compliance of rowers: implications for combined aer-
2009;107:127–134. doi: 10.1007/s00421-009-1110-x obic and strength training on arterial elasticity. Am J Physiol Heart Circ
59. Collier SR, Kanaley JA, Carhart R Jr, Frechette V, Tobin MM, Hall Physiol. 2006;290:H1596–H1600. doi: 10.1152/ajpheart.01054.2005
AK, Luckenbaugh AN, Fernhall B. Effect of 4 weeks of aerobic or resist- 73. Figueroa A, Park SY, Seo DY, Sanchez-Gonzalez MA, Baek YH.
ance exercise training on arterial stiffness, blood flow and blood pressure Combined resistance and endurance exercise training improves arterial
in pre- and stage-1 hypertensives. J Hum Hypertens. 2008;22:678–686. stiffness, blood pressure, and muscle strength in postmenopausal women.
doi: 10.1038/jhh.2008.36 Menopause. 2011;18:980–984. doi: 10.1097/gme.0b013e3182135442
60. MacDougall JD, McKelvie RS, Moroz DE, Sale DG, McCartney N, 74. Nakamura Y, Yamamoto N, Sakai K, Takano T. Antihypertensive effect
Downloaded from http://ahajournals.org by on October 5, 2020

Buick F. Factors affecting blood pressure during heavy weight lifting of sour milk and peptides isolated from it that are inhibitors to angio-
and static contractions. J Appl Physiol (1985). 1992;73:1590–1597. doi: tensin I-converting enzyme. J Dairy Sci. 1995;78:1253–1257. doi:
10.1152/jappl.1992.73.4.1590 10.3168/jds.S0022-0302(95)76745-5
61. Cortez-Cooper MY, Anton MM, Devan AE, Neidre DB, Cook JN, 75. Yoshizawa M, Maeda S, Miyaki A, Misono M, Choi Y, Shimojo N,
Tanaka H. The effects of strength training on central arterial compli- Ajisaka R, Tanaka H. Additive beneficial effects of lactotripeptides and
ance in middle-aged and older adults. Eur J Cardiovasc Prev Rehabil. aerobic exercise on arterial compliance in postmenopausal women.
2008;15:149–155. doi: 10.1097/HJR.0b013e3282f02fe2 Am J Physiol Heart Circ Physiol. 2009;297:H1899–H1903. doi:
62. Maeda S, Otsuki T, Iemitsu M, Kamioka M, Sugawara J, Kuno S, 10.1152/ajpheart.00433.2009
Ajisaka R, Tanaka H. Effects of leg resistance training on arterial func- 76. Yoshizawa M, Maeda S, Miyaki A, Misono M, Choi Y, Shimojo N,
tion in older men. Br J Sports Med. 2006;40:867–869. doi: 10.1136/bjsm. Ajisaka R, Tanaka H. Additive beneficial effects of lactotripeptides in-
2006.029538 take with regular exercise on endothelium-dependent dilatation in
63. Casey DP, Pierce GL, Howe KS, Mering MC, Braith RW. Effect of postmenopausal women. Am J Hypertens. 2010;23:368–372. doi:
resistance training on arterial wave reflection and brachial artery 10.1038/ajh.2009.270