JACC
HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK
QUICK SEARCH:   [advanced]


     

J Am Coll Cardiol, 2006; 48:790-797, doi:10.1016/j.jacc.2006.04.078 (Published online 21 July 2006).
© 2006 by the American College of Cardiology Foundation
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
j.jacc.2006.04.078v1
48/4/790    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Petersen, S. E.
Right arrow Articles by Channon, K. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Petersen, S. E.
Right arrow Articles by Channon, K. M.

CLINICAL RESEARCH: EXERCISE

Functional and Structural Vascular Remodeling in Elite Rowers Assessed by Cardiovascular Magnetic Resonance

Steffen E. Petersen, MD, DPhil*,{dagger},*, Frank Wiesmann, MD*,{dagger}, Lucy E. Hudsmith, MA, MRCP*,{dagger}, Matthew D. Robson, PhD*,{dagger}, Jane M. Francis, DCCR, DNM*,{dagger}, Joseph B. Selvanayagam, DPhil, FRACP*,{dagger}, Stefan Neubauer, MD, FRCP*,{dagger} and Keith M. Channon, MD, FRCP{dagger}

* University of Oxford Centre for Clinical Magnetic Resonance Research, Oxford, United Kingdom
{dagger} Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.

Manuscript received February 26, 2006; revised manuscript received March 4, 2006, accepted April 4, 2006.

* Reprint requests and correspondence: Dr. Steffen E. Petersen, University of Oxford Centre for Clinical Magnetic Resonance Research, Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom. (Email: steffen.petersen{at}cardiov.ox.ac.uk).


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
OBJECTIVES: We aimed to noninvasively quantify the effects of chronic exercise training on both peripheral and central conduit artery function and structure with high-resolution magnetic resonance imaging (MRI).

BACKGROUND: Physical activity has well-known beneficial effects on vascular function in subjects with endothelial dysfunction. Exercise also leads to beneficial effects on endothelial function in elderly athletes, possibly contributing toward the reduced risk from coronary artery disease in this age group. However, conflicting data exist on the training effects in the younger population.

METHODS: A total of 49 young (age 20 to 35 years) nonsmoking subjects, comprising elite rowers and age- and gender-matched sedentary control subjects, underwent MRI (1.5-T). The ascending, the proximal descending, and the distal descending aorta, and the common carotid artery and the brachial artery were assessed for diastolic and systolic area and distensibility. Endothelial-dependent and -independent brachial artery dilatation were also assessed by cine MRI.

RESULTS: Rowers showed vascular remodeling with enlarged brachial (by 51%, p < 0.001) and reduced central conduit artery cross-sectional areas (by up to 28% [e.g., distal descending aorta], p < 0.001). Vessel distensibilities (mm Hg–1) were similar for elite rowers when compared with sedentary control subjects at all levels of the aorta and the carotid and brachial artery (p > 0.05 for all). Endothelial-dependent dilation (percentage and mm2) was similar for rowers and control subjects (p > 0.05). However, rowers showed reduced absolute (by 33%) endothelial-independent dilation (p < 0.001).

CONCLUSIONS: Young elite rowers demonstrate normal endothelial-dependent but reduced endothelial-independent dilation. Chronic, whole body, combined endurance- and strength-training does not lead to changes in arterial stiffness but to vascular remodeling.

Abbreviations and Acronyms
  AA = ascending aorta
  cGMP = cyclic guanosine monophosphate
  DDA = distal descending aorta
  eNOS = endothelial nitric oxide synthase
  GTN = glyceryl trinitrate
  NO = nitric oxide
  PDA = proximal descending aorta

Endothelial dysfunction is a cardinal feature of vascular disease states, such as atherosclerosis (1), and is associated with an increased risk for cardiovascular events (2,3). Physical activity protects against the development of coronary artery disease (4), and a sedentary lifestyle is believed to contribute to approximately one-third of deaths caused by coronary artery disease (5).

There is mounting evidence that exercise has beneficial effects on endothelial function in subjects with endothelial dysfunction (i.e., with a priori impaired nitric oxide (NO)-related vasodilator function, such as in patients with arterial hypertension [6], hypercholesterolemia [7], obesity [8], diabetes [9], congestive heart failure [10], and coronary artery disease [11]). Similar beneficial effects of exercise training have been described for the physiological age-dependent decline of endothelial function (12,13), which might be due to reduced oxidative stress (14,15).

However, in healthy subjects, longitudinal and cross-sectional studies have produced conflicting data with regard to training effects on endothelial function (16–19). This might partly be explained by differences in exercise type (endurance vs. strength-training and combinations of both), because the NHANES (National Health And Nutrition Examination Study)-III has revealed differences in systemic markers of inflammation related to exercise type (20). Chronic exercise training seems to induce changes in caliber of skeletal muscle conduit arteries and resistance vessels via shear stress-mediated NO release both in animals (21) and humans (22). Exercise training increases endothelial nitric oxide synthase (eNOS) messenger ribonucleic acid and protein expression (23,24). However, improvement in endothelium-dependent vasodilator responses is a transient phenomenon (16–19,25) that is lost with long-term training (26). Chronic NO overproduction due to exercise training might be an explanation for this phenomenon, because prolonged treatment with glyceryl trinitrate (GTN), a direct NO donor, induces tolerance within 24 h to 48 h and the development of endothelial dysfunction (27,28). Indeed, constitutive overexpression of eNOS in the endothelium in transgenic mice results in resistance to the NO and cyclic guanosine monophosphate (cGMP)-mediated vasodilators via reduced soluble guanylate cyclase activity and decreased cGMP-dependent protein kinase protein levels (29). However, the effects of exercise-induced eNOS activation in the human vasculature remain unclear.

Accordingly, we sought to determine whether exercise training in healthy young adults is associated with vascular remodeling and functional evidence of altered vascular NO signaling. We used high-resolution noninvasive magnetic resonance imaging (MRI) to provide detailed characterization of vascular function and structure, including endothelial-dependent and -independent brachial artery dilation, aortic pulse wave velocities, and quantification of central and peripheral arterial distensibilities (30).


   Methods
Top
 Abstract
 Methods
Results
 Discussion
 References
 
Study population.   A total of 49 young (20 to 35 years of age) nonsmoking participants comprising 15 male elite rowers (mean age 24 ± 3 years, endurance- and strength-training 23 ± 7 h/week for 9 ± 5 years), 13 female elite rowers (mean age 24 ± 4 years, endurance- and strength-training 21 ± 4 h/week for 9 ± 6 years), and sedentary healthy control subjects (15 male, mean age 28 ± 2 years, and 6 female, mean age 28 ± 2 years) were enrolled into the study. A typical training program for the rowers comprised rowing at different expenditure levels in addition to 1 or 2 weight-lifting sessions. None of the subjects had received any vasoactive medication, and none had hypertension, diabetes, dyslipidemia, obesity (body mass index >25 kg/m2), coronary artery disease, or a family history of premature coronary artery or cerebrovascular disease. Subjects with contraindications for MRI were not enrolled. Table 1 highlights the expected differences in physiological characteristics between male and female and sedentary and rowing healthy subjects. The study was carried out according to the principles of the Declaration of Helsinki and was approved by our institutional committee on human research. Each subject gave informed written consent.


View this table:
[in this window]
[in a new window]
  		Table 1. Baseline Characteristics of Elite Rowers and Sedentary Healthy Control Subjects
 
MRI protocol.   Magnetic resonance imaging was performed on a 1.5-T clinical magnetic resonance scanner (Siemens Sonata, Erlangen, Germany) as described in detail previously (30). To exclude confounding effects on endothelial function, MRI was performed after a minimum of 20 min sitting rest and at a constant room temperature of 20°C. To summarize, the ascending aorta (AA), the proximal descending aorta (PDA), and the distal descending aorta (DDA) and the right common carotid artery (CCA) were assessed for diastolic and systolic area, absolute and relative area change, aortic and carotid artery distensibility, and the stiffness index, with steady-state free precession cine sequences with an in-plane resolution and slice thickness of 1.97 mm and 7 mm for the aorta and 0.52 mm and 3 mm for the carotid artery (Fig. 1). Blood pressure was measured from the left arm with a brachial arm sphygmomanometer during distensibility measurements of the aorta and carotid arteries and during brachial artery imaging.


Figure 1
View larger version (126K):
[in this window]
[in a new window]
  		Figure 1 Magnetic resonance imaging of vascular distensibility and diastolic vessel areas. Vessel wall tracings in diastolic (A, solid ellipse) and systolic (B, dashed ellipse) cine steady-state free precession images in the ascending aorta (AA) and proximal descending aorta (PDA). Diastolic images of distal descending aorta (DDA) (C), right common carotid artery (CCA) (D), and right brachial artery (BA) (E) in a rower. IJV = internal jugular vein; PT = pulmonary trunk; SCM = sternocleidomastoid muscle; SVC = superior vena cava.

 
A high-resolution gradient-echo pulse sequence with a velocity-encoding gradient for phase contrast MRI with a temporal resolution of 11 mm was applied to assess peak velocities (AA, PDA, and DDA); forward, reverse, and net aortic flow (AA); and to determine proximal (comprising the AA and the aortic arch) and distal pulse wave velocities in the descending aorta.

Flow-mediated or endothelial-dependent dilation was assessed in the right brachial artery comparing cross-sectional baseline diastolic brachial artery areas with those acquired 1 min after reactive hyperemia induced by release of a forearm cuff inflated to suprasystolic pressure for 4.5 min. Endothelial-independent brachial artery dilation was determined as the brachial artery area change compared with baseline 3 min after sublingual application of 400 µg GTN. For these measurements, a cardiac-gated steady-state free precession cine sequence was applied.

Image analysis.   As previously described in detail (30), aortic artery, carotid artery, and brachial artery cross-sectional areas were determined by tracing the inner vessel boundaries in diastole and systole with CMR tools image post-processing software (developed by Imperial College, University of London, United Kingdom). These areas were used to calculate absolute and relative area change within the cardiac cycle and to determine distensibility (relative change in cross-sectional area for a given pressure change) and stiffness index (ratio of logarithm systolic/diastolic pressures to relative change in cross-sectional area) at each vessel site (30–32). Flow measurements were performed with Argus Software (Siemens). Pulse wave velocities (m/s) were calculated by dividing the distance between measurement levels by time difference between the arrivals of the pulse waves at these levels. Arrival time of the pulse wave at each level was defined as the time point when the mean velocity reached one-half its maximum value (30,33).

Statistical analysis.   All data are presented as mean values ± SD unless stated otherwise. An independent-samples t test was used to test for differences between baseline characteristics of athletes and sedentary control subjects. All quantitative measures of vascular structure and function were compared between the groups with 2-way analysis of covariance, adjusting for gender as a fixed effect and body surface area as a covariate. The Spearman correlation coefficient was calculated to investigate the relation between brachial artery area and endothelial-dependent and -independent dilatation. Throughout the analyses, a 2-sided p value of <0.05 was considered statistically significant. All computations were performed with SPSS 11.5 (SPSS Inc., Chicago, Illinois).


   Results
Top
 Abstract
 Methods
 Results
Discussion
 References
 
Study population.   Sedentary control subjects and elite rowers (age range 20 to 35 years) differed in some baseline characteristics (Table 1), such as height and body surface area, as expected. The blood pressure amplitude (pulse pressure) was significantly increased in rowers compared with control subjects (p < 0.001), mainly owing to lower diastolic blood pressures (p < 0.001). A lower resting heart rate was observed in rowers compared with sedentary control subjects (p = 0.02), demonstrating the expected effect of exercise training.

Vascular remodeling after chronic whole body exercise training.   Diastolic aortic artery areas were similar in the ascending aorta (p = 0.4) but smaller in athletes compared with sedentary control subjects in the proximal (p = 0.001) and distal descending aorta (p < 0.001). Similarly, a smaller right common carotid artery diastolic area was observed (p = 0.031). In contrast to these findings in the central conduit arteries, rowers had 51% increased diastolic peripheral conduit artery areas (brachial artery) compared with control subjects (p < 0.001) (Fig. 2).


Figure 2
View larger version (24K):
[in this window]
[in a new window]
  		Figure 2 Comparison of diastolic vessel areas between young sedentary control subjects and young elite rowers quantified by magnetic resonance imaging at (A) different sites of the aorta and (B) in the right common carotid artery (CCA) and in the right brachial artery (BA). Two-way analysis of covariance, adjusting for gender as a fixed effect and body surface area as a covariate. Solid bars = sedentary control subjects; open bars = rowers. *p < 0.01; **p < 0.001. Other abbreviations as in Figure 1.

 
Aortic blood flow and pulse wave velocity.   Flow and pulse wave velocity data are presented in Table 2. Aortic forward flow per cardiac cycle was increased by 24% in rowers compared with sedentary control subjects (68 ± 21 ml vs. 55 ± 17 ml; p = 0.03), whereas the aortic flow output/min remained similar (p = 0.15), possibly owing to the lower heart rate in athletes. Peak blood velocities were similar in rowers at all three levels of the aorta: rowers versus control subjects in the ascending aorta 1.4 ± 0.4 m/s versus 1.2 ± 0.2 m/s (p = 0.57), in the proximal descending aorta 1.4 ± 0.3 m/s versus 1.2 ± 0.2 m/s (p = 0.16), and in the distal descending aorta 1.2 ± 0.2 m/s versus 1.1 ± 0.2 m/s (p = 0.13). Similarly, the proximal and distal pulse wave velocity were not different in rowers and control subjects (p = 0.82 and p = 0.57, respectively).


View this table:
[in this window]
[in a new window]
  		Table 2. Blood Flow, Blood Velocity, and Pulse Wave Velocity of Elite Rowers and Sedentary Control Subjects
 
Aortic, carotid, and brachial artery distensibility.   There were no differences in vessel distensibility in the ascending, proximal descending, and distal descending aorta, and the right carotid artery and the brachial artery between rowers and sedentary control subjects (Fig. 3). Similarly, no differences were observed at all vascular sites for stiffness index, another vascular stiffness parameter less dependent on the difference observed in pulse pressure between rowers and sedentary control subjects (data not shown).


Figure 3
View larger version (18K):
[in this window]
[in a new window]
  		Figure 3 Comparison of vascular distensibility between young sedentary control subjects and young elite rowers quantified by magnetic resonance imaging at (A) different sites of the aorta, (B) in the right common carotid artery (CCA), and (C) in the right brachial artery (BA). Two-way analysis of covariance, adjusting for gender as a fixed effect and body surface area as a covariate. Solid bars = sedentary control subjects; open bars = rowers. Other abbreviations as in Figure 1.

 
Endothelial-dependent and -independent brachial artery dilation.   To assess endothelial-dependent and -independent vasodilation, we quantified the brachial artery cross-sectional area in response to hyperemia-induced shear stress (flow-mediated dilatation) or the direct NO donor, GTN, respectively. Both relative endothelial-dependent and -independent dilatation were inversely correlated with vessel size (r = –0.52, p = 0.001 and r = –0.82, p < 0.001, respectively). In contrast, both absolute endothelial-dependent and -independent dilatation were not significantly correlated with vessel size (p = 0.29 and p = 0.19, respectively). Similarly, vessel-size–adjusted measures of endothelial-dependent and -independent dilatation (brachial artery diameter multiplied by the baseline radius [34]) did not show any significant correlations (p > 0.05 for both correlations) and revealed similar findings (not shown) to both relative and absolute endothelial-dependent and -independent dilatation presented in this article. Both absolute and relative endothelial-dependent dilatation responses in rowers were not significantly increased compared with control subjects (control subjects vs. rowers 1.8 ± 0.9 mm vs. 2.0 ± 1.4 mm, p = 0.35; 15.2 ± 8.4% vs. 11.4 ± 8.7%, p = 0.11, respectively). In contrast, both absolute and relative endothelial-independent brachial artery dilation were significantly reduced in rowers (control subjects vs. rowers 6.3 ± 1.6 mm vs. 4.2 ± 1.5 mm, p = 0.001; 52.4 ± 18.4% vs. 25.3 ± 14.2%, p < 0.001, respectively) (Fig. 4). The ratio of endothelial-dependent to the endothelial-independent brachial artery dilation was higher in rowers compared with sedentary control subjects (46.4 ± 25.3% vs. 28.1 ± 15.0%; p = 0.015).


Figure 4
View larger version (21K):
[in this window]
[in a new window]
  		Figure 4 Relative cross-sectional area changes induced by (A) hyperemia (flow-mediated dilation [FMD] representing endothelium-dependent relaxation) and by (B) glyceryl trinitrate (GTN) (endothelium-independent relaxation). (C) Ratio of FMD- to GTN-induced dilation. Similar results were obtained for the absolute cross-sectional area changes (data in text), a parameter independent of vessel size. Two-way analysis of covariance, adjusting for gender as a fixed effect and body surface area as a covariate. Solid bars = sedentary control subjects; open bars = rowers. *p < 0.01; **p < 0.001.

 

   Discussion
Top
 Abstract
 Methods
 Results
 Discussion
References
 
With high-resolution MRI, we investigated effects of chronic high-intensity, whole body, combined strength and endurance exercise training in young adults on peripheral and central conduit artery function and structure. We find that young adult elite rowers show no change in endothelial-dependent, flow-mediated, brachial artery dilation in comparison with control subjects. In contrast, endothelial-independent brachial artery dilation is greatly decreased in athletes compared with sedentary control subjects, with a corresponding increase in endothelial-dependent, flow-mediated, brachial artery dilation when expressed as a proportion of endothelial-independent brachial artery dilation. These observations might suggest that chronic exercise in healthy humans increases endothelial NO production but that this increase is accompanied by smooth muscle cell desensitization to NO. Another explanation for our findings could be a longer diffusion distance for exogenous NO across a potentially thicker smooth muscle cell layer in rowers.

We observed vascular remodeling to chronic exercise both in the peripheral and central conduit arteries, with the exception of the ascending aorta. Interestingly, in rowers, the more muscular, peripheral conduit arteries (brachial arteries) were enlarged, whereas the more elastic, proximal and distal descending aorta and the common carotid artery showed the novel finding of being smaller. Chronic exercise training seems to induce increases in arterial caliber in humans both in skeletal muscle conduit and resistance vessels (22). Animal work suggests that this might be an adaptive structural change to shear stress-mediated NO release (21). The finding of reduced vessel areas in rowers in the central conduit arteries conflicts with findings by Miyachi et al. (22). This longitudinal study observed unchanged blood flows in the aorta accompanied by an enlargement in aortic cross-sectional areas after an 8-week cycling training in men. The disparity in findings might be explained by different types of sport and duration of exercise. The opposing effects on vascular remodeling in the brachial artery and the central conduit arteries might be partly related to the differences in structural composition, with an enlarged, predominantly muscular brachial artery and smaller, predominantly elastic aorta and carotid artery. However, the mechanisms leading to reduced aortic areas in young elite rowers and the long-term implications of this inverse vascular remodeling remain unknown.

Vessel size has an important inverse relationship to both flow-mediated and GTN-induced brachial artery dilatation, as indicated by our own data and as demonstrated previously (34). The observed difference in brachial artery area between the sedentary control subjects and rowers highlights this as a potential pitfall in data interpretation. In contrast to the relative flow-mediated and GTN-induced brachial artery dilatation, the absolute area changes in our data sets are independent of baseline brachial artery area. According to an elegant study by Silber et al. (34), the flow-mediated dilatation (diameter change in millimeters) has an inverse relationship to the radius of the vessel. We have attempted to adjust for the dependence of vessel size in our dataset by calculating the relative flow-mediated dilatation in millimeters of vessel diameter change multiplied by the vessel radius. These results are not presented in this manuscript but have confirmed the data shown for relative and absolute endothelial-dependent and -independent brachial artery dilatation.

A large body of evidence suggests that endothelial dysfunction can be improved by physical activity (7–11,35), whereas the training effects on endothelial function in subjects with normal baseline endothelial function are inconsistent (12,16–19). Possible explanations for disparities among these studies include differences in types of sport (endurance- versus strength-training, lower versus upper versus whole body exercise) and in training intensity and duration. Furthermore, 2 studies even revealed adverse training effects on vascular function in volunteers with high-intensity exercise (36,37). Our findings now add significant new insights into the effects of exercise on the healthy human vasculature by demonstrating that exercise increases shear-stress induced NO release. The reduced endothelial-independent dilatation observed in rowers might be explained by 1 of 2 mechanisms. Chronic increases in NO production might lead to desensitization of smooth muscle relaxation (biochemical problem). Alternatively, the smooth muscle cell layer in rowers could potentially be thicker compared with sedentary control subjects, which could lead to a reduced response to exogenous NO owing to a longer diffusion distance (biomechanical problem). Accordingly, net flow-mediated dilatation responses in trained subjects appear no different than those of control subjects. Our findings suggest, for the first time, that the phenomenon of "tolerance" to NO might occur in healthy humans as a physiological mechanism. Several studies have reported a time-dependent increase of eNOS messenger ribonucleic acid and protein expression in experimental models and humans, but no study has shown that increased NO-mediated endothelial function is sustained in healthy subjects undertaking chronic exercise. Indeed, chronic overexpression of eNOS can lead to reduced NO-mediated vascular relaxation via resistance to cGMP-mediated vasodilators (29). Munzel et al. (27,28) and Schulz et al. (38) have demonstrated in elegant experimental work and in patients with coronary artery disease that tolerance and cross-tolerance to chronic GTN treatment might be caused by GTN-induced, oxygen-derived radical production, which might in turn inactivate the NO released from GTN and from the endothelium. Thus, NO overproduction in chronic exercise training might lead to similar desensitization via changes in NO signaling mediated through cGMP and/or oxygen radical production (37).

Large artery stiffness, measured as arterial distensibility, determines pulse pressure. We found increased pulse pressure in young rowers but normal peripheral and central conduit artery distensibility and arterial stiffness indices. This suggests that the difference in pulse pressure observed might be due to other factors in our study, such as difference in height (39). Aerobic or endurance exercise seems to be associated with reduced arterial stiffness in young healthy volunteers (40,41). In contrast, there is evidence that resistance- or strength-training might lead to reduced arterial distensibility (42). On the basis of these findings, unchanged conduit artery distensibility in our athletes might reflect the combined but opposing effects of endurance- and strength-training. Although central pressures have been similar in competitive endurance athletes and recreationally active subjects (43), one cannot necessarily rule out a source of error by calculating all vessel distensibilities with the pulse pressure based on noninvasive brachial artery blood pressure measurements.

We demonstrated increased resting aortic forward flow in the ascending aorta by almost 25% in rowers compared with sedentary control subjects. The well-known cardiac adaptations in athletes with increased stroke volumes (44) and reduced heart rates might contribute to these altered flow patterns in the aorta. Miyachi et al. (22) similarly reported increased blood flow in the ascending aorta, and in keeping with our study, the mean and peak velocities in the ascending aorta remained unchanged in this study investigating effects of an 8-week endurance cycling program.

Pulse wave velocity is an important parameter for arterial stiffness (32) and is now measured reliably and noninvasively by MRI in the aortic arch and the descending aorta, previously not accessible to ultrasound. We found no training effect on pulse wave velocities in the proximal aorta, comprising the ascending aorta and the aortic arch, and in the descending aorta. Pulse wave velocity is known to increase with age, and Gates et al. (45) showed reduced arterial stiffness (i.e., reduced pulse wave velocity) of endurance training in middle-aged and older subjects but not in the young. The discrepancy between their findings and ours might be explained by the fact that they measured the pulse wave velocities between the ascending aorta and the femoral artery and not separately for proximal and distal aorta. Miyachi et al. (46) measured the peripheral arm pulse wave velocity and found no difference between strength-trained athletes and sedentary control subjects. A recent study suggests an adverse effect of strength-training in women on central pulse wave velocity (between carotid and femoral artery) but not on peripheral, femoral-ankle pulse wave velocity (47).

Study limitations.   This study was designed to be noninvasive to avoid recruitment problems of young elite rowers concerned about anti-doping regulations. Consequently, we are unable to provide further proof of concept of our findings, such as vessel size-adjusted, dose-response curves of GTN-induced brachial artery dilatation or determination of isoprostanes or nitrates in the blood/urine.

In conclusion, our findings in chronic high-intensity, whole body, strength- and endurance-trained young adult elite athletes indicate normal endothelial and vascular peripheral and central conduit artery function, consistent with the notion that beneficial training effects on vascular function are only temporary. Chronic whole body exercise leads to vascular remodeling with increased areas of the peripheral muscular conduit arteries but reduced areas in central, more elastic, conduit arteries. The increased brachial artery dimension might reflect an adaptive structural change to mitigate exercise-related initial overproduction of endothelial NO. The implications of the novel finding of reduced central conduit artery areas in rowers remain to be defined. Noninvasive MRI bears the potential to study peripheral and central conduit artery function and structure in detail, and future studies might allow further insight into effects of physical activity, possibly as an adjunct to medical treatment, on endothelial dysfunction.


   Footnotes
 
This study was supported by grants from the German Academic Exchange Service (to Dr. Petersen), the British Heart Foundation (to Drs. Petersen, Hudsmith, Selvanayagam, and Neubauer), and the Wellcome Trust (to Drs. Wiesmann and Neubauer). Drs. Petersen and Wiesmann contributed equally to this work. Sadly, our colleague, friend, and co-author Frank Wiesmann died recently.


   References
Top
 Abstract
 Methods
 Results
 Discussion
 References
 

  1. Ross R. Atherosclerosis—an inflammatory disease N Engl J Med 1999;340:115-126.[Free Full Text]
  2. Halcox JP, Schenke WH, Zalos G, et al. Prognostic value of coronary vascular endothelial dysfunction Circulation 2002;106:653-658.[Abstract/Free Full Text]
  3. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease Circulation 2000;101:1899-1906.[Abstract/Free Full Text]
  4. Ornish D, Brown SE, Scherwitz LW, et al. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial Lancet 1990;336:129-133.[CrossRef][ISI][Medline]
  5. Francis K. Physical activity in the prevention of cardiovascular disease Phys Ther 1996;76:456-468.[Abstract/Free Full Text]
  6. Higashi Y, Sasaki S, Kurisu S, et al. Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjectsrole of endothelium-derived nitric oxide. Circulation 1999;100:1194-1202.[Abstract/Free Full Text]
  7. Walsh JH, Yong G, Cheetham C, et al. Effects of exercise training on conduit and resistance vessel function in treated and untreated hypercholesterolaemic subjects Eur Heart J 2003;24:1681-1689.[Abstract/Free Full Text]
  8. Woo KS, Chook P, Yu CW, et al. Effects of diet and exercise on obesity-related vascular dysfunction in children Circulation 2004;109:1981-1986.[Abstract/Free Full Text]
  9. Maiorana A, O’Driscoll G, Cheetham C, et al. The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes J Am Coll Cardiol 2001;38:860-866.[Abstract/Free Full Text]
  10. Hornig B, Maier V, Drexler H. Physical training improves endothelial function in patients with chronic heart failure Circulation 1996;93:210-214.[Abstract/Free Full Text]
  11. Hambrecht R, Wolf A, Gielen S, et al. Effect of exercise on coronary endothelial function in patients with coronary artery disease N Engl J Med 2000;342:454-460.[Abstract/Free Full Text]
  12. Rywik TM, Blackman MR, Yataco AR, et al. Enhanced endothelial vasoreactivity in endurance-trained older men J Appl Physiol 1999;87:2136-2142.[Abstract/Free Full Text]
  13. Gerhard M, Roddy MA, Creager SJ, Creager MA. Aging progressively impairs endothelium-dependent vasodilation in forearm resistance vessels of humans Hypertension 1996;27:849-853.[Abstract/Free Full Text]
  14. DeSouza CA, Shapiro LF, Clevenger CM, et al. Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men Circulation 2000;102:1351-1357.[Abstract/Free Full Text]
  15. Taddei S, Galetta F, Virdis A, et al. Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes Circulation 2000;101:2896-2901.[Abstract/Free Full Text]
  16. Green DJ, Fowler DT, O’Driscoll JG, Blanksby BA, Taylor RR. Endothelium-derived nitric oxide activity in forearm vessels of tennis players J Appl Physiol 1996;81:943-948.[Abstract/Free Full Text]
  17. Green DJ, O’Driscoll JG, Blanksby BA, Taylor RR. Effect of casting on forearm resistance vessels in young men Med Sci Sports Exerc 1997;29:1325-1331.[ISI][Medline]
  18. Clarkson P, Montgomery HE, Mullen MJ, et al. Exercise training enhances endothelial function in young men J Am Coll Cardiol 1999;33:1379-1385.[Abstract/Free Full Text]
  19. Kingwell BA, Sherrard B, Jennings GL, Dart AM. Four weeks of cycle training increases basal production of nitric oxide from the forearm Am J Physiol 1997;272:H1070-H1077.
  20. King DE, Carek P, Mainous 3rd AG, Pearson WS. Inflammatory markers and exercisedifferences related to exercise type. Med Sci Sports Exerc 2003;35:575-581.[CrossRef][ISI][Medline]
  21. Gollob MH, Green MS, Tang AS, et al. Identification of a gene responsible for familial Wolff-Parkinson-White syndrome N Engl J Med 2001;344:1823-1831.[Abstract/Free Full Text]
  22. Miyachi M, Iemitsu M, Okutsu M, Onodera S. Effects of endurance training on the size and blood flow of the arterial conductance vessels in humans Acta Physiol Scand 1998;163:13-16.[CrossRef][ISI][Medline]
  23. Hambrecht R, Adams V, Erbs S, et al. Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase Circulation 2003;107:3152-3158.[Abstract/Free Full Text]
  24. Laufs U, Werner N, Link A, et al. Physical training increases endothelial progenitor cells, inhibits neointima formation, and enhances angiogenesis Circulation 2004;109:220-226.[Abstract/Free Full Text]
  25. Delp MD, Laughlin MH. Time course of enhanced endothelium-mediated dilation in aorta of trained rats Med Sci Sports Exerc 1997;29:1454-1461.[ISI][Medline]
  26. Kingwell BA, Arnold PJ, Jennings GL, Dart AM. Spontaneous running increases aortic compliance in Wistar-Kyoto rats Cardiovasc Res 1997;35:132-137.[Abstract/Free Full Text]
  27. Munzel T, Heitzer T, Kurz S, et al. Dissociation of coronary vascular tolerance and neurohormonal adjustments during long-term nitroglycerin therapy in patients with stable coronary artery disease J Am Coll Cardiol 1996;27:297-303.[Abstract]
  28. Munzel T, Sayegh H, Freeman BA, Tarpey MM, Harrison DG. Evidence for enhanced vascular superoxide anion production in nitrate tolerance. A novel mechanism underlying tolerance and cross-tolerance J Clin Invest 1995;95:187-194.[ISI][Medline]
  29. Yamashita T, Kawashima S, Ohashi Y, et al. Mechanisms of reduced nitric oxide/cGMP-mediated vasorelaxation in transgenic mice overexpressing endothelial nitric oxide synthase Hypertension 2000;36:97-102.[Abstract/Free Full Text]
  30. Wiesmann F, Petersen SE, Leeson PM, et al. Global impairment of brachial, carotid, and aortic vascular function in young smokersdirect quantification by high-resolution magnetic resonance imaging. J Am Coll Cardiol 2004;44:2056-2064.[Abstract/Free Full Text]
  31. Oliver JJ, Webb DJ. Noninvasive assessment of arterial stiffness and risk of atherosclerotic events Arterioscler Thromb Vasc Biol 2003;23:554-566.[Abstract/Free Full Text]
  32. O’Rourke MF, Staessen JA, Vlachopoulos C, Duprez D, Plante GE. Clinical applications of arterial stiffness; definitions and reference values Am J Hypertens 2002;15:426-444.[CrossRef][ISI][Medline]
  33. Groenink M, de Roos A, Mulder BJ, Spaan JA, van der Wall EE. Changes in aortic distensibility and pulse wave velocity assessed with magnetic resonance imaging following beta-blocker therapy in the Marfan syndrome Am J Cardiol 1998;82:203-208.[CrossRef][ISI][Medline]
  34. Silber HA, Ouyang P, Bluemke DA, Gupta SN, Foo TK, Lima JA. Why is flow-mediated dilation dependent on arterial size? Assessment of the shear stimulus using phase-contrast magnetic resonance imaging Am J Physiol Heart Circ Physiol 2005;288:H822-H828.[Abstract/Free Full Text]
  35. Higashi Y, Sasaki S, Sasaki N, et al. Daily aerobic exercise improves reactive hyperemia in patients with essential hypertension Hypertension 1999;33:591-597.[Abstract/Free Full Text]
  36. Bergholm R, Makimattila S, Valkonen M, et al. Intense physical training decreases circulating antioxidants and endothelium-dependent vasodilatation in vivo Atherosclerosis 1999;145:341-349.[CrossRef][ISI][Medline]
  37. Goto C, Higashi Y, Kimura M, et al. Effect of different intensities of exercise on endothelium-dependent vasodilation in humansrole of endothelium-dependent nitric oxide and oxidative stress. Circulation 2003;108:530-535.[Abstract/Free Full Text]
  38. Schulz E, Tsilimingas N, Rinze R, et al. Functional and biochemical analysis of endothelial (dys)function and NO/cGMP signaling in human blood vessels with and without nitroglycerin pretreatment Circulation 2002;105:1170-1175.[Abstract/Free Full Text]
  39. London GM, Guerin AP, Pannier B, Marchais SJ, Stimpel M. Influence of sex on arterial hemodynamics and blood pressure. Role of body height Hypertension 1995;26:514-519.[Abstract/Free Full Text]
  40. Cameron JD, Dart AM. Exercise training increases total systemic arterial compliance in humans Am J Physiol 1994;266:H693-H701.
  41. Kingwell BA, Cameron JD, Gillies KJ, Jennings GL, Dart AM. Arterial compliance may influence baroreflex function in athletes and hypertensives Am J Physiol 1995;268:H411-H418.
  42. Miyachi M, Kawano H, Sugawara J, et al. Unfavorable effects of resistance training on central arterial compliancea randomized intervention study. Circulation 2004;110:2858-2863.[Abstract/Free Full Text]
  43. Edwards DG, Lang JT. Augmentation index and systolic load are lower in competitive endurance athletes Am J Hypertens 2005;18:679-683.[CrossRef][ISI][Medline]
  44. Petersen SE, Selvanayagam JB, Francis JM, et al. Differentiation of athlete’s heart from pathological forms of cardiac hypertrophy by means of geometric indices derived from cardiovascular magnetic resonance J Cardiovasc Magn Reson 2005;7:551-558.[ISI][Medline]
  45. Gates PE, Tanaka H, Graves J, Seals DR. Left ventricular structure and diastolic function with human ageing. Relation to habitual exercise and arterial stiffness Eur Heart J 2003;24:2213-2220.[Abstract/Free Full Text]
  46. Miyachi M, Donato AJ, Yamamoto K, et al. Greater age-related reductions in central arterial compliance in resistance-trained men Hypertension 2003;41:130-135.[Abstract/Free Full Text]
  47. Cortez-Cooper MY, DeVan AE, Anton MM, et al. Effects of high intensity resistance training on arterial stiffness and wave reflection in women Am J Hypertens 2005;18:930-934.[CrossRef][ISI][Medline]




This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
j.jacc.2006.04.078v1
48/4/790    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Petersen, S. E.
Right arrow Articles by Channon, K. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Petersen, S. E.
Right arrow Articles by Channon, K. M.

HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK