1. 1
Blood Pressure Responses to Small and Large Muscle Dynamic
Exercise in Older Adults of Different Aerobic Fitness Level
Dustin M. Grinnell, Joaquin U. Gonzales, and David N. Proctor*
Noll Laboratory, Department of Kinesiology, Pennsylvania State University, University Park, PA
*Corresponding Author:
David N. Proctor, Ph.D.
Associate Professor of Kinesiology, Physiology and Medicine
105 Noll Laboratory, The Pennsylvania State University
University Park, PA 16802
Phone: 814-863-0724 Fax: 814-865-4602
Email: dnp3@psu.edu
Study funded in part from NIH grant R01 AG018246 to D.N. Proctor.
Running Head: Pressor responses, active muscle mass, and aging

2. 2
ABSTRACT
The aim of this study was to compare the blood pressure responses to two modes of
dynamic exercise in older lower fit vs. higher fit men and women. It was hypothesized that 1)
systolic blood pressures would increase more during small muscle mass exercise than large
muscle and 2) aerobic fitness would influence the blood pressure response in older adults in a
mode or sex-specific manner. Older (60-80 yrs) normotensive healthy men (higher fit n=12,
lower fit n=6) and women (higher fit n=13, lower fit n=12) were recruited. All subjects
performed treadmill and single-leg knee extensor exercise to fatigue on separate days. Systolic
and diastolic blood pressure were monitored during exercise and mean arterial blood pressure
was calculated by equation. The rise in blood pressure with exercise was quantified by slope
analysis using blood pressures during Stage 1 through 4 for each exercise mode. To normalize
the pressor response to exercise intensity the absolute pressures were normalized to METs
(multiples of resting oxygen uptake). Results indicated that all groups exhibited higher arterial
pressure responses during knee extensor exercise as compared to treadmill exercise. Fitness level
did not influence these responses during treadmill exercise, but did attenuate the rise in systolic
blood pressure during knee extensor exercise in older men, but not older women. In summary
these findings suggest that small muscle dynamic exercise elicits a higher blood pressure
response as compared to large muscle and fitness influences the response to small muscle mass
exercise in men but not in women.
Keywords: sex differences, pressor response

3. 3
INTRODUCTION
Dynamic exercise is accompanied by increases in arterial blood pressure that are
mediated by increased central command as well as feedback from active skeletal muscles (i.e.,
group III and IV afferents that are sensitive to mechanical and metabolic changes, respectively).
Arterial blood pressure during exercise is modulated by arterial baroreflexes that adjusts
sympathetic nerve activity within active and inactive skeletal muscle (1). The rise in blood
pressure with exercise serves to increase or maintain blood flow, but the pressor response can be
exaggerated in conditions associated with endothelial dysfunction (2-4).
Blood pressure responses to dynamic exercise are influenced by the size of active muscle
(5-6) such that the magnitude of the pressor reflex is inversely related to the size of active muscle
(7). Therefore, with respect to dynamic exercise, the blood pressure response to the use of a
large muscle mass has been shown to be less pronounced when compared to small muscle
activity (8-11). It is well known that this higher response with respect to the small muscle mass
exercise is far greater than the metabolic cost of the exercise. The observable difference exists
largely because of the whole body cardiovascular adjustments to the exercise stress (12). Large
muscle dynamic exercise elicits a large rise in heart rate and cardiac output accompanied by a
marked decline in total resistance (TPR). The reduction in TPR as a result of the systemic
vasodilatation to the large working muscle mass is the primary cause for the whole body decline
in blood pressure. During an exercise which involves the contraction and relaxation of only a
small muscle mass, there are only modest increases in heart rate and cardiac output accompanied
by little or no change in TPR. Because a large vasodilatory response is not stimulated, TPR does
not markedly decrease, and the blood pressure response does not fall dramatically.

4. 4
It is well known that age is associated with a rise in resting and exercise blood pressure.
With respect to resting blood pressure there is, on average, a 20 mm Hg systolic and 10 mm Hg
diastolic increment increase in blood pressure from age 30 to 65 years (13). In a cross-sectional
study of 10,355 people the average systolic pressure in those aged >65 years was 140 mmHg for
men and 150 mmHg for women; the average diastolic pressure was 70 mmHg in men and 80
mmHg in women (14). With regard to exercise much research has shown that there is a
heightened blood pressure response (especially systolic blood pressure) to graded dynamic
exercise in older men and women when compared to younger men and women (15). In addition,
it has also been found that this heightened BP response is more pronounced in older women (16).
It is well-known that training provides blood pressure lowering benefits with both normotensive
and hypertensive individuals (17-19) as well as for older individuals (20) during rest and exercise.
The purpose of the current investigation was to explore the systolic, diastolic, and mean
arterial blood pressure responses - defined by the slope values: absolute blood pressure across
working METs - to two modes of dynamic exercise in older men and women of different fitness
levels. Firstly, we wanted to conduct a focused observation on how the pressor responses
compared between two modes of dynamic work and ask whether the response was determined by
the active muscle, i.e. whether it might be more pronounced during knee extensor exercise
compared to treadmill in the aged. Secondly, we wanted to know if the heightened exercise
blood pressure response normally seen in older individuals was fitness dependent, i.e. to
determine if an increase in fitness level modulates the heightened blood pressure response seen
in older men and women, and if this fitness effect is mode or sex-specific.

5. 5
METHODS
Participants
Six lower fit older men (71 ± 2 yr), 12 higher fit older men (71 ± 2 yr), 12 lower fit older
women (67±1 yr), and 13 higher fit older women (67±1 yr) were recruited for this study. All
participants were normotensive (< 140/90 mmHg), and were apparently healthy as evaluated by
medical history questionnaire, a physical examination, and resting electrocardiogram. All
participants provided written consent to participate in the study after receiving an explanation of
the experimental procedures and possible risks associated with participation. This study was
approved by the Office for Research Protections at Pennsylvania State University in agreement
with the guidelines set forth by the Declaration of Helsinki.
Treadmill Exercise Testing
Each participant performed a modified Balke treadmill test to peak effort. This graded
test consisted of a 4 minute warm-up at 2.5 mph followed by adjustment of the speed to elicit
~75% of age-predicted peak heart rate after which the intensity of exercise increased every 2
minutes (2% increase in elevation) until the participants reached volitional fatigue.
Blood pressures were measured via auscultation during the second minute of each
exercise stage. Blood pressure measurements were not attempted during peak effort to enable
participants to fully engage both arms and give maximum effort without disturbance. Pulmonary
oxygen uptake (VO2) was measured using analysis of expired gases by a Parvomedics metabolic
cart (Sandy, Utah).
Knee Extensor Exercise

6. 6
Each participant performed single leg knee extensor exercise as described previously (21-
22). To begin, participants were seated in a semi-reclined position with knees flexed at an angle
of 90. To avoid extraneous movement during the exercise participant’s torso and thighs were
strapped to the chairs. Knee extensions through a nearly full range of motion (90–170) were
performed at 40 contractions per minute with the left foot placed in a boot that was connected to
the pedal arm of a cycle ergometer (Monark) that was placed behind the subject. The exercise
protocol consisted of three minute stages. The first stage consisted of quiet rest, followed by
unloaded passive exercise (manual external movement of lower leg), knee extensions against no
resistance (0 W), and finally extensions as resistance increased incrementally until the subject
could no longer maintain cadence. After each three minute stage work rate increased by 10 W for
men and 5 W for women.
Blood pressures were measured continuously at rest and during exercise using radial
tonometry of the right hand by a Finometer MIDI (Finapress Medical Systems, Netherlands).
The blood pressure waveform at rest was calibrated against multiple measurements taken by an
IntelliSense blood pressure monitor (Omrom, Vernon Hills, Illinois). Beat by beat blood pressure
was collected on-line at a sampling frequency of 400 Hz and stored using a Powerlab system
(ADInstruments, Castle Hill, Australia).
Data Analysis and Computations
All blood pressure calculations were derived from average values taken over the last 30
seconds of rest, passive exercise, and each work rate. Slope values were calculated using blood
pressure values taken during exercise (treadmill: between stages 1 and 4; knee kick: first 4
stages). Those participants who did not complete as least three stages were not included in the
slope analysis.

7. 7
Statistical Analysis
Significance was accepted at P < 0.05 for all statistical analyses. Microsoft Excel was
used to perform all analyses. A one-tailed paired t-test was used to test for mode-specific
differences. A two-sample independent t-test was used to test for significant between group
differences.

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RESULTS
Descriptive Characteristics (Table 1)
Anthropometric characteristics of the participants are presented in Table 1. Higher and
low fit men were similar age, but lower fit women were older than higher fit women (P <0.05).
Both higher and low fit groups were of similar weight and height, however, the lower fit group
had a higher percent body fat than the higher fit within each sex (P <0.05).
Peak Exercise Responses (Table 2)
Table 2 displays group average data for peak exercise responses divided by mode of
exercise. As a result of study design the lower fit group had a lower peak aerobic capacity (peak
VO2) during treadmill exercise than the higher fit group within each sex (P <0.05). Similarly, the
peak VO2 (ml/kg/min) and work rate achieved during knee extensor exercise was lower in the
lower fit group as compared to the higher fit group within each sex (P <0.05). The difference in
peak VO2 during knee extensor exercise showed sex-specific differences based on the
expression of VO2.
Influence of the active muscle mass on the pressor response
Relationships between the arterial blood pressure responses to both modes of dynamic
exercise are displayed in Figure 1. Blood pressure increased during both small muscle and large
muscle exercises in all groups. This pressor response was significantly (P <0.05) more
pronounced during knee extension exercise as compared to treadmill exercise in older men
(Figure 1A) and older women (Figure 1B) independent of fitness level.
Influence of fitness and sex on pressor response in older adults

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Fitness did not influence the blood pressure response to treadmill exercise. Thus, a higher
BP response was not observed in low fit older adults vs. high fit older adults irrespective of sex.
During knee extension exercise fitness influenced the pressor response in older adults in a
sex-specific manner such that lower fit older men had a higher blood pressure response than
higher fit men (P <0.05). This observation was not found for women (P = 0.17).

10. 10
DISCUSSION
In the present investigation we examined the arterial blood pressure responses to graded
dynamic exercise in older (60-79 yr) normotensive groups of women and men. Consistent with
prior research involving healthy younger individuals, we observed greater intensity-dependent
increases in systolic and mean pressures during small muscle mass dynamic exercise (single leg,
knee extensor exercise) compared to whole body dynamic exercise (standardized treadmill
testing). Aerobic fitness attenuated the rise in systolic and mean pressures during small muscle
mass exercise in older men, but had no apparent influence on these responses during large
muscle mass exercise in either sex. Moreover, aerobic fitness level had no measurable influence
on pressor responses to either large or small muscle mass exercise in older women. Collectively,
these are novel findings which have implications for understanding the determinants of, and
potential countermeasures for, sex-specific age differences in blood pressure reactivity to
exercise.
Pressor responses to dynamic exercise: Influence of active muscle size
All subjects exhibited larger exercise pressor responses, defined as the total rise in SBP
and MAP per MET through 3 (women) or 4 (men) stages, during knee extensor exercise than
those observed during treadmill exercise. This finding is not surprising given that 1) arterial
pressure during dynamic exercise is thought to be regulated primarily as a function of relative
work intensity (Bezucha et al 1982; Lewis et al 1983, 1985; etc) and 2) that a one-MET increase
during knee extensor exercise represents a much larger % of an individual’s working range
during that mode of exercise (peak METS = ___ to ___) compared to treadmill exercise (peak
METS = __ to __). However, even when mode differences in peak metabolic capacity in the

11. 11
present study were accounted for (SBP or MAP vs. % of mode-specific VO2peak or peak METS),
the mode differences in exercise blood pressures persisted in all four groups IS THIS TRUE?
We will also want to know if the slopes of the SBP and MAP responses vs. % of VO2peak
differ between modes (overall and within groups)….the reason for this will become clearer
below).
No prior studies have directly compared cardiovascular responses to graded knee
extensor and treadmill exercise to allow comparisons with the present findings. However, the
greater blood pressure responses observed during single knee extensor exercise in the present
study (across all groups) are likely reflective of a greater use of accessory (stabilizing) muscles;
such an influence could elevate arterial pressure by central (greater volitional effort, HR) and/or
peripheral (vascular compression and metaboreflex stimulation) mechanisms. Further insight
into the former possibility will be explored by comparing the HR response (rise in HR per unit
increase in VO2 or MET) to knee extensor exercise in relation to the HR response to treadmill
testing. If the overall HR response to knee extensor exercise is exaggerated (and if the RPE vs. %
of peak workload relationship is steeper during knee extensor vs. treadmill exercise; Stebbins et
al AJP 2002), this would support the interpretation that greater pressor responses during knee
extensor exercise are due, at least in part, to greater recruitment and/or isometric involvement of
stabilizing muscles.
Pressor responses to large muscle dynamic exercise: influence of fitness
Systolic, diastolic and mean arterial blood pressures of aerobically trained young adults
are generally lower at any given submaximal (same absolute) workload or VO2 compared to their

12. 12
sedentary peers; this reflects a reduction in total systemic vascular resistance since cardiac output
at a given submaximal workload does not change with aerobic training (refs). Exaggerated
pressor responses at submaximal exercise loads have been observed in adults with a higher
proportion of fast-twitch, low oxidative fibers in their leg musculature (ref) and in younger adults
at risk for future hypertension (i.e., familial hypertension) who also have low calf muscle
vasodilatory capacities (Bassett et al), suggesting a possible link between exercise blood pressure
and the structural and/or functional capacity of the leg muscles to vasodilate in young (currently
normotensive) adults. It is important to note that most of the literature examining these
relationships in younger adults has been conducted in men; relatively little is known about the
determinants of exercise blood pressure in younger women (confirm that this statement is true,
Martin et al included younger fit and sedentary women).
Several studies have reported lower blood pressure responses at fixed submaximal
workloads in aerobically trained compared to sedentary, but normotensive older men (Hagberg et
al 1985; Ogawa et al 1992; Martin et al 1991). Martin et al (ref) for example, observed 15-18%
lower systolic, and 10 to 14% lower mean blood pressures at the same submaximal treadmill
stages in aerobically trained vs. untrained older men (a smaller, but significant fitness effect was
observed in their younger men as well). In the current study, we did not observe a significant
fitness difference in blood pressure responses to treadmill exercise in older men, when expressed
as a unit change in blood pressure per MET (figure) (is this true when we look at BP responses
vs. treadmill VO2?). The lack of a significant fitness effect on submaximal blood pressure
responses to treadmill testing in the present groups of older men is difficult to explain, but could
reflect a) the relatively low sample size of our low-fit older group, b), the lack of a significant
age group difference in the first place (data for younger groups not shown) and/or c) the higher

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resting systolic and mean arterial pressures of the higher fit older group (vs. all other groups;
Table 1; we may need to control for resting BP differences via ANCOVA).
Blood pressures at similar relative work intensities were not significantly influenced by
fitness in older men (figure), consistent with most of the literature for both weight bearing
(Ogawa et al 92; Martin et al 1991, etc) and non-weight bearing (Hagberg et al 1985?, Proctor et
al Mayo study) exercise. However, it is interesting to note that the rise in MAP at 80% of
treadmill VO2max (i.e., delta increase from rest) appeared to be markedly less (insert p-value) in
our higher men than it was in our lower fit older men. Collectively, this comparison reflects the
importance of taking resting (baseline) blood pressure and relative exercise intensity into account
when interpreting the pressor responses to exercise in older adults.
There was no fitness effect on treadmill exercise blood pressure responses in older
women, regardless of how the data were examined or analyzed. The lack of an aerobic fitness
effect on blood pressures of older women during submaximal exercise is consistent with results
of Ogawa et al (ref). In their study, systolic, diastolic and mean pressures during Bruce treadmill
stages 1 and 2 were no different in older fit vs. sedentary women, despite the markedly elevated
responses of these groups compared to younger controls (ref). Our older female groups were
relatively similar in age, body size and composition, and cardiorespiratory fitness (treadmill
VO2max per kg FFM; will need to check each of these statements) to the subjects studied by
Ogawa et al (ref) and similar mean arterial pressures at comparable work intensities (is this
statement true?....compare their data at Bruce protocol stage 1 and 2 vs. our data at similar
MET levels). However, these findings appear to be at odds with the results of a large cross-
sectional study of women (Kokkinos et al 2002) in which fitness level (age-adjusted treadmill
time to exhaustion) was a significant determinant of systolic blood pressure at a fixed

14. 14
submaximal workload (Bruce protocol stage 2 = 6-7 METS). Reasons for such disparate
findings are unclear, but the inclusion of an extremely wide age range of participants in the
Kokkinos et al study (20 to 80 yr) could obscure the influence of fitness on pressor responses in
older women per se. Aerobic exercise training programs sufficient to significantly increase
systemic aerobic capacity (treadmill VO2max) generally do result in improved hemodynamic
responses (i.e., reduced arterial pressures and rate pressure product) to exercise in younger and
middle-aged women (find refs), but the findings in studies of exclusively older, post-menopausal
women have been less consistent and often show attenuated cardiac (Spina et al papers) and local
vascular (Martin et al 1991) adaptations to conventional aerobic exercise training interventions.
Martin et al suggested that the remediative effects of aerobic training on vascular function might
depend on the presence of estrogen since a sub-sample of their subjects who had taken estrogen
therapy exhibited slightly lower exercise blood pressures and higher muscle dilator capacities
than the estrogen deficient women did. Thus, the lack of any apparent fitness modulation on
hemodynamic responses during large muscle mass exercise in the older estrogen deficient
women we studied was not entirely unexpected.
Pressor responses to small muscle dynamic exercise: influence of fitness
The literature on aging and blood pressure responses to small muscle mass exercise are
limited primarily to isometric contractions of the forearm musculature in men (Taylor et al 1991;
Petrofsky & Lind 1975). In those studies, the magnitude of rise in arterial pressure during
sustained contractions at 40% of maximum voluntary handgrip force was very similar in healthy
younger compared to older men matched for peak forearm strength. Differences in active

15. 15
muscle groups (arm vs. leg), type of contraction (static vs. dynamic), and aging-related muscle
function (preserved vs. reduced) between the present study and that of Taylor et al (ref) make it
very difficult to compare findings. Nonetheless, it was interesting to find evidence in the present
study for a fitness effect in the older men, but not in their female peers during dynamic knee
extensor exercise. Why fitness would exert a greater influence on the pressor responses to
graded knee extensor vs. treadmill exercise in older men is not immediately obvious, nor is the
lack of such an influence in older women. However, the relatively large systolic and especially
diastolic pressure responses to isolated quadriceps exercise in older low-fit women (figure 1)
suggests a greater hemodynamic load on their heart (compared to higher fit women and men)
during activities that specifically stress this functionally important muscle group (Kokkinos et al
ref, etc; we should also examine rate pressure product as an index of myocardial O2
demand).
ACKNOWLEDGEMENTS
The authors would like to thank the participants,
GRANTS
This research was supported by National Institute on Aging Grant (NIA) R01 AG-
0182446 (to D.N. Proctor, and Division of Research Resources Grant M01 RR-10732 (to GCRC).

16. 16
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Table 1. Participant characteristics
Men Women
Higher Fit Lower Fit Higher Fit Lower Fit
(n=12) (n=7) (n=13) (n=12)
Age (yr) 63.8 ± 1.1 66.3 ± 2.3 63 ± 1 68.3 ± 1.8*
Weight (kg) 79.8 ± 3.3 82.1 ± 4.3 63.3 ± 1.6 64 ± 2.8
Height (cm) 178 ± 1.9 175 ± 1.9 161.3 ± 2.1 160.9 ± 1.4
Body fat (%) 20.5 ± 1.1 25.6 ± 1.2* 32.4 ± 0.8 37 ± 1.5*
Fat free mass (kg) 61.4 ± 1.9 59.5 ± 2.6 44.2 ± 2.1 39.3 ± 1.3
Quadriceps mass (kg) 2.5 ± 0.1 2.4 ± 0.2 1.8 ± 0.1 1.8 ± 0.1
Blood Pressure (mmHg)
Resting Systolic 134.8 ± 2.7 122.4 ± 2.8* 129.1 ± 4.1 129.2 ± 4.6
Resting Diastolic 80.8 ± 1.4 76.9 ± 2.0 72.3 ± 1.8 73.2 ± 3.6
Resting Mean Arterial 98.8 ± 1.8 91.9 ± 2.4* 91.2 ± 8.9 91.8 ± 3.3
Values are mean ± SEM. *, significant difference between high and lower fit older adults within each sex
(P < 0.05).
Table 2. Peak exercise responses
Men Women
Higher Fit Lower Fit Higher Fit Lower Fit
(n=12) (n=7) (n=13) (n=12)
Treadmill
VO2 (L/min) 3.2 ± 0.1 2.3 ± 1.3* 2.0 ± 0.1 1.5 ± 0.1*
VO2 (ml/kg/min) 40.2 ± 1.4 28.2 ± 1.5* 31.2 ± 0.8 23.2 ± 0.7*
VO2 (ml/min/kg FFM) 52 ± 1.8 39 ± 2.3* 45.6 ± 2.2 37.5 ± 1.1*
Knee Kick
Final work rate (Watts) 46.7 ± 2.2 36.7 ± 4.2* 30 ± 1.5 24.2 ± 1.7*
VO2 (L/min) 0.92 ± 0.03 0.75 ± 0.03* 0.61 ± 0.03 0.55 ± 0.04
VO2 (ml/kg/min) 11.6 ± 0.5 9.1 ± 0.3* 9.7 ± 0.3 8.7 ± 0.4*
VO2 (ml/min/kg QMM) 36.8 ± 1.8 31.9 ± 2.2* 35.4 ± 2.1 31.9 ± 1.8
Values are mean ± SEM. VO2: oxygen uptake; FFM: fat free mass; QMM: quadriceps muscle mass. *,
significant difference between high and lower fit older adults within each sex (P ≤ 0.05).

19. 19
FIGURE LEGENDS
Figure 1 The rise in blood pressure (systolic blood pressure, SBP) across METs during treadmill
and knee extensor exercise. (A) The pressor response was higher during knee extensor as
compared to treadmill exercise. There was no difference in the rise of blood pressure between
low fit (n=6) and higher fit (n=12) men during treadmill exercise, but lower fit old men had a
higher blood pressure response to knee extensor exercise than high fit men. (B) The pressor
response was higher during knee extensor as compared to treadmill exercise. There was no
difference in the rise of blood pressure between low fit (n=12) and high fit (n=13) women during
treadmill and knee extensor exercise. *, significant difference between treadmill and knee
extensor exercise (P < 0.05). †, significant difference between low and high fit older men (P <
0.05).
M en W om en
60 60
T re a d m ill T re a d m ill
*
50
K n e e E x te n s o r
*,† 50
K n e e E x te n s o r
S B P S lo p e (S B P v s . M E T )
S B P S lo p e (S B P v s . M E T )
*
40 40
30 * 30
20 20
10 10
0 0
O M (H F ) O M (L F ) O W (H F ) O W (L F )
A g e G ro u p A g e G ro u p