AJH

2004; 17:314 320

Exaggerated Exercise Blood

Pressure Is Related to Impaired
Endothelial Vasodilator Function
Kerry J. Stewart, Jidong Sung, Harry A. Silber, Jerome L. Fleg,
Mark D. Kelemen, Katherine L. Turner, Anita C. Bacher, Devon A. Dobrosielski,
James R. DeRegis, Edward P. Shapiro, and Pamela Ouyang
Background: Persons with high normal blood pressure (BP) or mild hypertension who also have an exaggerated BP response to exercise are at risk for worsening
hypertension. The mechanisms that explain this relationship are unknown. We examined the relationships of endothelial vasodilator function and of aortic stiffness with
exercise BP.
Methods: Subjects were 38 men and 44 women, aged
55 to 75 years, with untreated high normal BP or mild
hypertension but otherwise healthy. Exercise was performed on a treadmill. Endothelial vasodilator function
was assessed as brachial artery flow-mediated vasodilation
(FMD) during reactive hyperemia. Aortic stiffness was
measured as pulse wave velocity (PWV).
Results: Among men, resting systolic BP explained
34% of the variance (P .01) in maximal exercise systolic BP and FMD explained an additional 11% (P .01);
resting systolic BP explained 23% of the variance in
maximal pulse pressure (PP) (P .01), and FMD ex-

plained an additional 10% (P .01). Among women,

resting systolic BP was the only independent correlate of
maximal systolic BP (R2 0.12, P .03) and FMD
correlated negatively with maximal PP (R2 0.12, P
.03). Among men, FMD was the only independent correlate of the difference between resting and maximal systolic
BP (R2 0.20, P .02). The FMD was the only independent correlate of the difference between resting and
maximal PP among men (R2 0.17, P .03) and among
women (R2 0.12, P .03). The PWV did not correlate
with exercise BP responses.
Conclusions: These results suggest that impaired endothelial vasodilator function may be a mechanism contributing to exercise hypertension and may also be one link
between exaggerated exercise BP and worsening
hypertension. Am J Hypertens 2004;17:314 320
2004 American Journal of Hypertension, Ltd.
Key Words: Hypertension, exercise, blood pressure,
pulse pressure, endothelium, aortic stiffness, stress test.

ersons with normal or mildly elevated blood pressure (BP) who exhibit an exaggerated exercise BP
are at increased risk for worsening hypertension.13 However, the mechanisms that explain this relationship are unknown. Impaired endothelial vasodilator
function occurs in small resistance arteries,4,5 and in small
and large conduit arteries.6 Impaired endothelial vasodilation during exercise might contribute to an exaggerated

exercise BP response. Abnormal endothelial function may

promote the growth of vascular smooth muscle,7 leading
to arterial stiffening. Arterial stiffening with aging reduces
the ability of the arterial tree to buffer the increase in
systolic BP generated by left ventricular ejection.8 These
factors contribute to resting hypertension.
This study evaluated the relationship of BP responses to
exercise with endothelial vasodilator function and aortic

Received January 13, 2003. First decision February 20, 2003. Accepted
June 11, 2003.
From the Department of Medicine, Division of Cardiology, Johns
Hopkins School of Medicine (KJS, JS, MDK, KLT, ACB, DAD, JRD,
HAS, EPS, PO), Baltimore, Maryland; and Gerontology Research Center, National Institute on Aging, National Institutes of Health (JLF),
Baltimore, Maryland.
Dr. Sung is presently affiliated with the Division of Cardiology,
Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
Dr. Fleg is presently affiliated with the National Heart, Lung, and

Blood Institute, National Institutes of Health, Bethesda, Maryland.

0895-7061/04/$30.00
doi:10.1016/S0895-7061(03)01003-3

Dr. Kelemen is presently affiliated with the Department of Medicine,

Division of Cardiology, University of Maryland School of Medicine,
Baltimore, Maryland.
This study was supported by a grant from the National Institutes of
Health, R01HL59164 (KJS) and the Johns Hopkins Bayview General
Clinical Research Center (5M01RR02715).
Address correspondence and reprint requests to Dr. Kerry J. Stewart,
Johns Hopkins Bayview Medical Center, 4940 Eastern Avenue, Baltimore, MD 21224; e-mail: kstewart@mail.jhmi.edu
2004 by the American Journal of Hypertension, Ltd.
Published by Elsevier Inc.

AJHApril 2004 VOL. 17, NO. 4

EXERCISE BLOOD PRESSURE AND ENDOTHELIAL FUNCTION

stiffness in a sample of men and women at risk for worsening hypertension. A finding that these mechanisms are
associated with exercise BP would suggest common abnormalities linking exaggerated exercise BP with worsening hypertension. Because of potential gender differences
in endothelial vasodilator function9 and exercise capacity,
these relationships were also examined by gender.

Methods
Study Population
This analysis was performed on baseline measurements in
men and women recruited for an exercise training study.
They were aged 55 to 75 years and had untreated high
normal BP or mild hypertension, defined by the 1997 Joint
National Committee of Detection, Evaluation, and Treatment of High BP10 as systolic BP of 130 to 139 mm Hg or
diastolic BP of 85 to 89 mm Hg as high normal and
systolic BP of 140 to 159 mm Hg or diastolic BP of 90 to
99 mm Hg as mild hypertension.
The exclusion criteria were: 1) medications for hypertension; 2) cardiovascular diseases, such as coronary heart
disease, peripheral arterial disease, and congestive heart
failure; 3) electrocardiographic abnormalities indicative of
myocardial infarction or heart block; 4) diabetes, renal
disease, and hepatic disease; 5) cigarette smoking in the
previous 6 months; and 6) moderate exercise 3 to 6
metabolic equivalents for 30 min per day, 3 times per
week. Women using hormone replacement therapy (HRT)
were eligible. A screening exercise test excluded subjects
with ischemic electrocardiographic changes (horizontal or
downsloping ST-segment depression 1 mm), complex
dysrhythmias, or symptoms of ischemia.
Informed consent was obtained from each subject. The
protocol was approved by our Institutional Review Board.
Resting BP
Resting BP was measured in the brachial artery using a
Dinamap MPS Select (Johnson & Johnson, New Brunswick, NJ). After 5 min of sitting rest, BP was measured
three times with 1 min between measurements. If the
readings differed by 5 mm Hg, extra readings were obtained. The average of three consecutive measurements
within 5 mm Hg of each other was the examination value.
Subjects were seen at weekly visits, and were required to
have systolic BP between 130 and 159 mm Hg or diastolic
BP between 85 and 99 mm Hg during two consecutive
visits, and an average BP in the same range over four
visits. An additional BP was obtained on a separate visit
after the subject qualified for the study. The average of all
of these visits was used as resting BP.
Endothelial Vasodilator
Function: Brachial Artery
Flow-Mediated Vasodilation
11

Following published guidelines, the images were obtained by the same examiner and analyzed by the same

315

reader in a blinded manner. Our intraobserver variability

for repeated measurements is 2% 1%. Subjects were
studied lying supine. The brachial artery was visualized
with a 10-MHz linear array transducer in the antecubital
space 2 cm above its bifurcation. A pressure cuff was
placed on the upper arm and inflated by a rapid inflator
(Hokanson E-10, D. E. Hokanson, Inc., Bellevue, WA) to
exceed systolic BP by 40 mm Hg. After 5 min the cuff was
rapidly deflated, and the brachial artery was imaged at 1
and 3 min later. A simultaneous electrocardiogram was
recorded. After 15 min of rest to allow the artery to return
to baseline, the baseline diameter was imaged before assessment of endothelium-independent nitroglycerin-mediated dilation. The subject was given 0.4 mg of sublingual
nitroglycerin, and the artery was imaged 3 and 5 min later.
Nitroglycerin was not given if the systolic BP was 100
mm Hg. The obtained images were analyzed using NIH
Image (http://rsb.info.nih.gov/nih-image). For each phase,
images of an arterial segment with clear intima were
selected at end-diastole as identified by the superimposed
R wave. Five diameter measurements were made on each
of three images at each phase and the average for all
measurements was calculated. For flow-mediated vasodilation (FMD), measurements were made at baseline, and 1
and 3 min after cuff deflation. The FMD was defined as the
highest observed percent change of brachial artery diameter from baseline. For nitroglycerin-mediated dilation
(NMD), measurements were made before nitroglycerin
administration and 3 and 5 min after nitroglycerin. The
NMD was the highest observed percent change in brachial
artery diameter from baseline.
Aortic Stiffness
Aortic stiffness was measured by pulse wave velocity
(PWV), using methods described elsewhere.12 Briefly, carotidfemoral PWV was calculated as distance/transit time
(in centimeters per second) of the pulse wave from the
base of the neck for the common carotid to the right
femoral artery. The pulse waves at each of these sites were
obtained simultaneously using Doppler probes. The distance traveled by the pulse waveform was measured over
the participants torso. The distance from the carotid to the
aortic site was subtracted from the sum of the aortic to the
umbilicus to the femoral site, to adjust for the opposite
direction of blood flow in that arterial branch. This methods reproducibility in our laboratory yields Pearson and
intraclass correlation coefficients of 0.90 and 0.88, respectively, between examiners.12
Blood Chemistry
Fasting blood samples were obtained for glucose, insulin,
and lipids.
Exercise Testing
Exercise was performed on a treadmill integrated with
a SensorMedics Vmax229 Metabolic and ECG system

316

EXERCISE BLOOD PRESSURE AND ENDOTHELIAL FUNCTION

(SensorMedics, Inc., Yorba Linda, CA). Subjects performed a modified Balke protocol, beginning at 3 mph, 0%
grade, and increasing 2.5% grade each 3 min until maximal volitional fatigue was reached. A 12-lead electrocardiogram was monitored continuously. Exercise BP was
measured during the last 30 sec of each stage using a
mercury column sphygmomanometer according to the
guidelines of the American College of Sports Medicine.13
Systolic BP was measured at phase I of the Korotkoff
sounds, and diastolic BP was measured between phases IV
and V. As needed, the subjects rested their hand on the
examiners shoulder to minimize movement artifact. The
Rating of Perceived Exertion using the Borg 6 to 20
scale14 was obtained during each stage, and a rating 18
was an indicator of maximal effort. The highest value of
oxygen uptake was considered peak.
Statistical Analysis
Data are expressed as mean SD. Gender comparisons
were made with Student t tests. Pearson correlation coefficients were calculated separately by gender to determine
bivariate correlates of exercise BP responses. Stepwise
regression was used to determine the independent contributions among parameters that showed a bivariate correlation with exercise BP responses. The variables analyzed
were not excessively skewed and did not require transformation. The level of statistical significance was set at P
.05.

Results
Thirty-eight men and 44 women were studied (Table 1).
Women were on average 2.6 years older than the men (P
.05). Fourteen women were using HRT. Total serum
cholesterol (P .05) and HDL (P .01) were higher
among women, whereas fasting glucose (P .05) was
higher among men. Baseline artery diameters and the
absolute maximal diameters of the artery after reactive
hyperemia and nitroglycerin were higher among men (all
P .01). Nonetheless, the maximal FMD as a percent
change in artery diameter and the maximal NMD were not
different between genders. There was no difference in
FMD or NMD, or any other variables of interest among
women using HRT compared with those who were not
(data not shown).
There was no gender difference in resting systolic BP,
but women had a lower diastolic BP (P .01), and thus,
a higher resting pulse pressure (PP) (P .01) (Table 2).
The maximal exercise systolic BP was higher among men
(P .01), whereas both genders achieved similar levels of
maximal diastolic BP. Thus, the maximal PP was higher
among men (P .01). The differences between resting
and maximal systolic BP and PP were higher among men
(both P .01), whereas the difference between resting and
maximal diastolic BP was higher among women (P
.01). Peak oxygen uptake was higher among men than

AJHApril 2004 VOL. 17, NO. 4

women (P .01). The values for maximal heart rate

indicate that both genders exerted a similar high degree of
effort during maximal testing. Aortic PWV did not differ
by gender.
Table 3 shows correlations of resting BP and of FMD
with exercise BP responses. Among men, resting systolic
BP correlated positively with maximal systolic BP (P
.01) and maximal PP (P .01); resting diastolic BP
correlated positively with maximal diastolic BP (P .01).
Among women, resting systolic BP correlated positively
with maximal systolic BP (P .03) and maximal diastolic
BP (P .02); resting diastolic BP correlated positively
with maximal diastolic BP (P .01) and negatively with
maximal PP (P .02). Among men, FMD correlated
negatively with maximal systolic BP (P .02). The FMD
correlated negatively with the magnitude of the difference
between resting and maximal exercise systolic BP among
men (P .01) but not among women. The FMD correlated negatively with maximal PP and negatively with the
difference between resting and maximal exercise PP in
both genders (all P .03).
The following results were also obtained (data not
shown). The NMD did not correlate with any measures of
resting or maximal BP or with the differences between
resting and maximal BP. Resting PP, a marker of arterial
stiffness, was not correlated with any exercise BP response. Correlations of aortic PWV with resting and with
exercise BP and PP responses were not significant in either
gender with Pearson correlation coefficients ranging from
R 0.18 to 0.17, and P values from .19 to .98. Age,
peak oxygen uptake, maximal exercise heart rate, insulin,
glucose, triglycerides, and cholesterol did not correlate
with exercise BP responses.
In stepwise regression models, among men, 34% of the
variance in maximal systolic BP was explained by resting
systolic BP and an additional 11% by FMD (P .01);
23% of the variance in maximal PP was explained by
resting systolic BP and an additional 10% by FMD (P
.01). The FMD was the only independent predictor of the
difference between resting and maximal exercise systolic
BP, explaining 20% of the variance (P .02) (Fig. 1). The
FMD was also the only independent predictor of the
difference between resting and maximal PP, explaining
17% of the variance (P .03). Among women, resting
systolic BP was the only independent predictor of maximal systolic BP explaining 12% of the variance (P .03);
FMD was the only independent predictor of the difference
between resting and maximal exercise PP explaining 12%
of the variance (P .03) (Fig. 1).
Resting diastolic BP was the only independent predictor of maximal diastolic BP, explaining 23% of the variance among men (P .01), and 36% of the variance
among women (P .01). The HRT was used in the
models for women and had no significant effect on any
variable.

AJHApril 2004 VOL. 17, NO. 4

EXERCISE BLOOD PRESSURE AND ENDOTHELIAL FUNCTION

317

Table 1. Subject characteristics, lipids, and brachial artery measurements

Variable
Age (y; range 5575)
Weight (kg)
BMI (kg/m2)
Total cholesterol (mg/dL)
LDL cholesterol (mg/dL)
HDL cholesterol (mg/dL)
Triglycerides (mg/dL)
Insulin (mg/dL)
Glucose (mg/dL)
Baseline diameter (mm)
Maximal diameter, reactive hyperemia (mm)
FMD maximal (%)
Baseline for NMD
Maximal diameter, nitrogylcerin (mm)
NMD maximal (%)

Men
(n 38)
62.1
92.5
29.4
207.1
136.8
43.1
139.2
10.7
106.1
4.8
5.1
6.7
4.9
5.4
10.3

5.4
15.8
3.5
31.8
27.7
8.2
61.7
5.4
10.3
0.7
0.7
5.4
0.5
0.6
6.0

Women
(n 44)
64.7
79
30.3
226.8
139.5
59.4
139.4
8.8
101
3.8
4.0
6.9
3.8
4.2
12.7

6*
15.2
5.4
44.7*
41.2
16.5
70.4
4
10.6*
0.3
0.6
5.7
0.6
0.6
7.3

BMI body mass index; FMD flow-mediated vasodilation; NMD nitrogylcerin-mediated vasodilation.
Values are mean SD
* Men versus women P .05; P .01.

Discussion
To our knowledge this is the first study to demonstrate the
extent to which systolic BP and PP increases during maximal exercise are associated with impaired endothelial
vasodilator function in the brachial artery. Notably, these
relationships were observed despite a narrow range of
resting BP in our subjects. In younger persons, exaggerated exercise systolic BP results primarily from a failure to
reduce total peripheral resistance during exercise15 and
may be related to early structural vascular changes that
precede progression to hypertension.16 Among our older
subjects, mean BP at rest, a marker of peripheral resistance
was not related to exercise BP. With advancing age, progressive arterial stiffness induces high systolic BP and a

widening of PP.17 We found no correlation of aortic PWV

or resting PP, both markers of arterial stiffness, with any
exercise BP response (data not shown). Some studies have
suggested a negative association of endothelial vasodilator
function with arterial stiffness measured by pulse wave
contour analysis,18,19 but we found no relationship of
FMD with PWV. Resting systolic BP, diastolic BP, PP,
and mean BP were not correlated with FMD or PWV. The
NMD, which is endothelium-independent and may reveal
abnormalities in smooth muscle function or arterial compliance in the presence of multiple risk factors for atherosclerosis,20 did not correlate with resting or exercise BP or
with FMD.
Although our findings appear to be contrary to studies

Table 2. Blood pressure and heart rate at rest, aortic pulse wave velocity, maximal exercise responses, and
blood pressure responses to exercise
Variable
Resting systolic BP (mm Hg)
Resting diastolic BP (mm Hg)
Pulse pressure rest (mm Hg)
Resting heart rate (beats/min)
Aortic pulse wave velocity (cm/sec)
Maximal oxygen uptake (mL/kg/min)
Maximal heart rate (beats/min)
Maximal treadmill duration (sec)
Maximal systolic BP (mm Hg)
Maximal diastolic BP (mm Hg)
Pulse pressure maximal (mm Hg)
Systolic BP rest-maximal difference (mm Hg)
Diastolic BP rest-maximal difference (mm Hg)
Pulse pressure rest-maximal difference (mm Hg)
Values are mean SD
* Men versus women P .01.

Men (n 38)
141.7
82
59.7
71.1
896.4
28
165.7
1002.1
231.4
97.3
134.1
90.3
15.1
75.2

8.8
5.8
7.7
9.2
227.5
4.2
13.2
216.9
21.3
11.2
20.9
17.8
9.9
17.4

Women (n 44)
141.6
73.8
67.8
72.5
996.5
20.9
163
657
217.8
98.8
119
76.2
25.3
50.9

8.7
8.4*
8.4*
7.1
305.2
3.1*
12.8
191.8*
19.6*
14
21*
18.5*
11.3*
18.8*

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EXERCISE BLOOD PRESSURE AND ENDOTHELIAL FUNCTION

AJHApril 2004 VOL. 17, NO. 4

Table 3. Pearson correlations of exercise blood pressure responses with resting blood pressure and flowmediated dilation
Men
Resting systolic BP
Maximal systolic BP
Systolic BP rest-maximal difference
Maximal diastolic BP
Diastolic BP rest-maximal difference
Maximal pulse pressure
Pulse pressure rest-maximal difference
Resting diastolic BP
Maximal diastolic BP
Diastolic BP rest-maximal difference
Maximal systolic BP
Systolic BP rest-maximal difference
Maximal pulse pressure
Pulse pressure rest-maximal difference
Flow-mediated dilation
Maximal systolic BP
Systolic BP rest-maximal difference
Maximal diastolic BP
Diastolic BP rest-maximal difference
Maximal pulse pressure
Pulse pressure rest-maximal difference

that have assessed relationships of FMD, NMD, and PWV

with BP in persons with hypertension, our subjects have
only milder forms of hypertension so that subtle abnormalities in these parameters and associations with BP were
not evident at rest. In contrast, a higher exercise BP
response was associated with impaired endothelium-dependent vasodilator function. Endothelium-dependent vasodilation in conduit arteries occurs in response to systolic
wall sheer stress during peak hyperemia.21 Therefore, it
seems likely that impaired endothelial function might limit
vasodilation in response to the sheer stress of exercise
hyperemia, thereby contributing to an exaggerated exercise BP response.

Women

r
r
r
r
r
r

0.58,
0.22,
0.22,
0.06,
0.48,
0.26,

P
P
P
P
P
P

.01
.23
.22
.72
.01
.15

r
r
r
r
r
r

.34,
.10,
0.38,
0.10,
0.06,
0.16,

P
P
P
P
P
P

.03
.52
.02
.54
.69
.32

r
r
r
r
r
r

0.48,
0.07,
0.19,
0.02,
0.06,
0.02,

P
P
P
P
P
P

.01
.72
.27
.93
.75
.91

r
r
r
r
r
r

0.60,
.03,
0.01,
0.22,
0.38,
0.21,

P
P
P
P
P
P

.01
.98
.92
.17
.02
.18

r
r
r
r
r
r

0.44,
0.44,
0.10,
0.06,
0.39,
0.42,

P
P
P
P
P
P

.02
.01
.57
.73
.03
.03

r
r
r
r
r
r

0.15,
0.22,
0.29,
0.23,
0.34,
0.35,

P
P
P
P
P
P

.34
.17
.06
.15
.03
.03

Impaired endothelial vasodilator function is not specific

to hypertension. It is also associated with aging, menopause, hyperlipidemia, smoking, diabetes, and hyperhomocysteinemia, and may be a common pathophysiologic
mechanism for developing atherosclerotic disease.22 A
novel finding of our study is that a higher exercise BP was
associated with decreased FMD, even in the absence of
overt or asymptomatic coronary disease, diabetes, or
smoking, and with adjustment for resting BP, lipids, and
HRT. Exercise hypertension is a marker for worsening
hypertension,13 a condition associated with impaired endothelial vasodilator function.6 Thus, our results in subjects with mild hypertension support the concept that

FIG. 1. Relationship of the difference between resting and maximal exercise systolic BP with flow-mediated dilation among men, r 0.44,
R2 0.20, P .01 (left), and the relationship of the difference between resting and maximal exercise PP with flow-mediated dilation in
women, r 0.35, R2 0.12, P .03 (right). SBP systolic blood pressure; PP pulse pressure.

AJHApril 2004 VOL. 17, NO. 4

EXERCISE BLOOD PRESSURE AND ENDOTHELIAL FUNCTION

impaired endothelial vasodilator function is a potential

cause, and not merely a consequence of hypertension.
Although brachial artery FMD provided only modest explanatory power for maximal exercise BP, endothelial
dysfunction is a systemic disease. Impaired endothelial
function in the smaller resistance vessels, which parallels
large artery vasoreactivity in hypertensive persons,6 may
have also contributed to the increased exercise BP responses. Because an estimated 90% of the US population
will develop hypertension,23 further research is needed to
confirm the relationship between exercise BP response and
FMD. Such research could further the development of
therapeutic strategies for hypertension aimed specifically
at the endothelium.
A few gender differences in the determinants of exercise BP response were noted. Resting systolic BP was the
strongest predictor of maximal exercise systolic BP in
both genders, and maximal exercise PP among men. Still,
FMD explained 10% of the variance in maximal systolic
BP and PP among men, and was the only independent
predictor of the difference between resting and maximal
exercise PP in both genders. Analyzing the data by gender
minimized the effect of gender differences in brachial
artery size as a determinant of the hyperemic shear stress
stimulus in FMD.21 We found no independent effect of
brachial artery size in either gender or any effect of HRT
use among women on the relationships of FMD with
exercise BP. However, the small number of women on
HRT reduces our statistical power to detect such differences. Although both genders had a substantial increase in
exercise systolic BP, men reached a higher exercise workload, which could help to explain their higher maximal
exercise systolic BP. Nevertheless, the associations of
exercise BP with FMD were independent of exercise capacity. Whereas women had a higher difference between
resting and exercise diastolic BP, their exercise diastolic
BP was not different from that of men. Although resting
diastolic BP was negatively associated with maximal PP
among women, FMD was also a negative correlate of
maximal PP among women. Taken together, these results
suggest that impairment in FMD provides independent,
albeit modest, explanatory power for the increase in systolic BP and PP during exercise in both genders.
Limitations
These cross-sectional data reveal associations between
FMD and exercise BP but do not elucidate cause and effect
mechanisms. Although impaired endothelial function may
be a novel mechanism that contributes to exercise hypertension, other explanations are possible. Higher BP responses on the treadmill may also mean higher BP during
routine daily activity. Hence, the greater overall pressure
load on the arteries may cause impaired endothelial function. The increased sympathetic activation that is seen in
the hypertensive state24 may also cause impaired FMD.
Chronically elevated sympathetic -adrenergic vasocon-

319

striction associated with aging also influences basal limb

blood flow and vascular conductance.25 Arterial wall
thickening in the early stages of resting hypertension is a
diffuse process,26 and may contribute to exaggerated exercise BP. Nonetheless, PWV was not related to resting or
exercise BP in this study.
Another possible explanation for increased exercise BP
is exaggerated PP amplification, which has been observed
in younger, physically active men.27 However, this explanation is less likely in our older, sedentary subjects. Our
carefully selected cohort minimized potential influences of
a wide age range, more severe hypertension, use of antihypertensive medications, and other disease conditions, on
exercise BP and FMD. Increasing age and established
hypertension are associated with impaired endothelial vasodilator function when examined across a broader range
of age and BP than our subjects.4 6,28 Thus, we cannot
elucidate whether the association of exercise BP with
FMD is a characteristic of aging, mild hypertension, or
both.
Other potential limitations relate to obtaining BP using
different methods. Resting BP was an average obtained
over several weeks using an automated sphygmomanometer. Maximal exercise BP was a single measurement
using a mercury column sphygmomanometer. Although
highly experienced observers obtained exercise BP following established methods,13 these are not as precise as
invasive methods and their reproducibility was not evaluated in this study. Regarding FMD, we did not measure the
initial blood flow in the brachial artery after release of the
BP cuff. The FMD was measured using established methodology,11 which assumes that 5 min of blood flow occlusion and subsequent release results in a reproducible
stimulus for reactive hyperemia. A few studies that have
used this method have shown equivalence in reactive
hyperemic blood flow when comparing normotensive versus hypertensive subjects and have demonstrated differences in FMD between these groups.29,30 We assume that
differences in FMD among our subjects resulted from
impairment of the endothelium rather than variations in
the sheer stress stimulus, but this cannot be definitively
verified. In addition, although every attempt is made to
measure the brachial artery at the same site at baseline and
after cuff release, a slight change in transducer position
may result in measurement error, and sometimes produces
a negative value as observed in a few subjects in the
present study.
In conclusion, we found that systolic BP and PP responses to maximal exercise are associated with impaired
endothelial vasodilator function, independent of resting
BP and arterial stiffness. Because so many adults are at
risk for hypertension, the results have broad clinical implications. If impaired endothelial vasodilator function is
established as a mediator of exercise hypertension, which
itself is a marker of progression to more severe hypertension, the endothelium may be a possible target for preventive intervention.

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EXERCISE BLOOD PRESSURE AND ENDOTHELIAL FUNCTION

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