VASCULAR ADAPTATION TO EXERCISE IN HUMANS:
THE ROLE OF HEMODYNAMIC STIMULI
DANIEL J GREEN
1,2
MARIA T.E. HOPMAN
3
JAUME PADILLA
4,5,6
M. HAROLD LAUGHLIN
6,7, 8
DICK H.J. THIJSSEN
1,3
1
Research Institute for Sport and Exercise Sciences, Liverpool John Moores University,
Liverpool, United Kingdom
2
School of Sport Science, Exercise and Health, The University of Western Australia,
Crawley, Western Australia
3
Radboud University Medical Center, Radboud Institute for Health Sciences,
Department of Physiology, Nijmegen, The Netherlands
4
Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO,
USA
5
Department of Child Health, University of Missouri, Columbia, MO, USA
6
Dalton Cardiovascular Research Center, University of Missouri, MO, USA
7
Department of Biomedical Sciences, University of Missouri, MO, USA
8
Department of Medical Pharmacology and Physiology, University of Missouri, MO, USA
Keywords: training; hemodynamic stimuli; cardiovascular; adaptation
Total number of words (text+references): 28,018
Title page+abstract+table of contents: 699
Figures: 8
Author for correspondence:
Winthrop Professor Daniel J. Green
School of Sports Science, Exercise and Health M408,
The University of Western Australia
Crawley, 6009, Australia
Phone: +61 8 6488 2361 Fax: +61 8 64881039
Green et al Exercise, hemodynamics and vascular adaptation
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ABSTRACT
On the 400
th
anniversary of Harvey’s Lumleian lectures, this review focusses on the impact
of physical exercise on “hemodynamic” forces associated with the movement of blood
through arteries in humans and the functional and structural adaptations that result from
repeated episodic exposure to such stimuli. The late 20
th
century discovery that endothelial
cells modify arterial tone via paracrine transduction, provoked studies exploring the direct
mechanical effects of blood flow and pressure on vascular function and adaptation in vivo. In
this review, we address the impact of distinct hemodynamic signals that occur in response to
exercise, the inter-relationships between these signals, the nature of the adaptive responses
that manifest under different physiological conditions and the implications for human health.
Exercise modifies blood flow, luminal shear stress, arterial pressure and tangential wall
stress, all of which can transduce changes in arterial function, diameter and wall thickness.
There are important clinical implications of the adaptation that occurs as a consequence of
repeated hemodynamic stimulation associated with exercise training in humans, including
impacts on atherosclerotic risk in conduit arteries, the control of blood pressure in resistance
vessels, oxygen delivery and diffusion, and microvascular health. Exercise training studies
have demonstrated that direct hemodynamic impacts on the health of the artery wall
contribute substantially to the well-established decrease in cardiovascular risk attributed to
physical activity.
Green et al Exercise, hemodynamics and vascular adaptation
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TABLE OF CONTENTS
I. INTRODUCTION: EXERCISE AND ARTERY HEALTH IN HUMANS
A. Impact of exercise and physical activity on cardiovascular risk
B. The risk factor gap: Traditional risk factors do not fully explain risk reduction
C. Evidence for a role of direct impacts of hemodynamic forces on vascular health
D. Integrative aspects of vascular adaptation to training
II. WHAT HEMODYNAMIC FORCES ARE RELEVANT IN THE VASCULATURE?
A. Pressure effects
i. Detection of cyclic circumferential strain by the endothelium
ii. Relevance of the pattern of cyclic circumferential strain
B. Endothelial shear stress
i. Detection of shear stress by the endothelium
ii. Relevance of the pattern of shear
C. Importance of interaction between hemodynamic forces
III. HEMODYNAMIC STIMULI DURING ACUTE EXERCISE
A. Effects of exercise on hemodynamic forces
i. Shear stress in vascular territories perfusing active areas
ii. Shear stress in vascular territories perfusing inactive areas: start of exercise
iii. What are the mechanisms for changes in shear stress at the start of exercise?
iv. Shear stress in vascular territories perfusing inactive areas: continuation of exercise
v. Non-shear stress hemodynamic stimuli mediating artery vasomotion during exercise
B. Impact of different shear stress patterns on artery function
IV. VASCULAR ADAPTATIONS TO EXERCISE TRAINING: ROLE OF
HEMODYNAMIC FACTORS
A. Adaptations in vascular function
i. Conduit arteries
ii. Resistance arteries
iii. Microcirculation
iv. Cutaneous microcirculation: an active vessel bed during exercise
B. Adaptation in vascular structure
i. Conduit arteries
ii. Resistance arteries
iii. Microcirculation
C. Changes in vascular cell gene expression induced by exercise training
V. WHICH FACTORS MODERATE THE ADAPTATION TO TRAINING?
A. Distinct adaptations to different forms of exercise training
B. Distinct time-course in adaptation in different vascular properties
C. Interaction between changes in function and structure
D. Impact of cardiovascular disease on hemodynamic stimuli and vascular adaptation to
exercise
VI. SUMMARY AND IMPLICATIONS FOR EXERCISE SCIENCE AND HEALTH
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We in the West are the first generation in human history in which the mass of the population
has to deliberately exercise to be healthy.
– Professor Jeremiah Morris (216) –
I. INTRODUCTION: EXERCISE AND ARTERY HEALTH IN HUMANS
Recent technological "advances" have fundamentally altered the vocational and lifestyle
behaviours of humans in the space of a few generations. Profound changes associated with
ubiquitous exposure to television, mobile communication devices and the internet have
rapidly accelerated an underlying trend in sedentary behaviour related to urbanisation,
automation and widespread use of the automobile (272). In global terms, it was recently
estimated that physical inactivity caused 6–10% of all deaths from the major non-
communicable diseases (coronary disease, type 2 diabetes, breast and colon cancers), or more
than 5.3 of the 57 million deaths that occurred worldwide. This equates to the number of
deaths attributable to tobacco (112).
Approximately 1/3
rd
of the global population do not meet minimum physical activity (PA)
requirements to sustain health (112). In the West, the impact of technological change on PA
levels and cardiovascular health is occurring on a background of unprecedented demographic
shifts associated with population ageing, raising the spectre of individuals experiencing more
years of frailty and compromised life quality, with associated increases in healthcare costs
(229). There has never been a more sedentary population of humans than the 21st century
Western society, prompting some to suggest that the positive historical trend in life
expectancy may soon be threatened (231). These observations reinforce the critical
importance of increasing physical activity levels and primary prevention is now a global
policy agenda (137).
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Although exercise programs may be regarded as an effective strategy to “compensate” for
loss of routine physical activity, better insight is required into the physiological adaptations to
distinct stimuli associated with exercise. This review focuses on the impact of exercise on
the vasculature, in particular, the direct effects mediated by physical, mechanical and/or
hemodynamic forces on arterial function, structure and adaptation in humans.
A. Impact of exercise and physical activity on cardiovascular risk
Retrospective studies strongly suggested that regular physical activity is associated with
lower risk for primary CV mortality and morbidity (197, 241). Subsequent prospective
studies provided direct evidence that adopting a physically active lifestyle delays all-cause
mortality, extends longevity (242) and reduces risk for CV mortality by 42-44%, compared to
persistently unfit men (28, 180). Furthermore, the relationship between physical activity and
CV risk exhibits a curvilinear dose-response pattern (319) with increasing, but diminishing,
returns at higher activity levels (210). It is important to acknowledge that, whilst fitness has
been regarded as a surrogate for habitual physical activity, these factors have independent and
overlapping roles in the prevention of cardiovascular disease (63). In those with heart disease,
exercise-based rehabilitation is associated with a reduction in CV mortality and fewer
hospital admissions (9). These benefits, in the context of both primary and secondary
prevention of CVD, approximate and may exceed those associated with antihypertensive
(308) or lipid lowering drugs (47, 203). Indeed, meta-epidemiological evidence (205
randomized controlled trials, n=339,274) found equal effectiveness of exercise training and
contemporary drug interventions (220), in terms of mortality reduction.