muscle strength influences pressor responses to static

. . . Published ahead of Print

Medicine & Science in Sports & Exercise® Published ahead of Print contains articles in unedited manuscript form that have been peer reviewed and accepted for publication. This manuscript will undergo copyediting, page composition, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered that could affect the content.

Copyright © 2017 American College of Sports Medicine

Muscle Strength Influences Pressor Responses to Static Handgrip

in Men and Women

Karambir Notay

1, Jordan B. Lee

1, Anthony V. Incognito

1,

Jeremy D. Seed1, Adam A. Arthurs

1, and Philip J. Millar

1,2

1Department of Human Health and Nutritional Sciences, University of Guelph, Guelph,

Ontario, Canada; 2

Toronto General Research Institute, Toronto General Hospital,

Toronto, Ontario, Canada

Accepted for Publication: 6 November 2017

Muscle Strength Influences Pressor Responses to Static Handgrip in Men and

Women

Karambir Notay1, Jordan B. Lee

1, Anthony V. Incognito

1,

Jeremy D. Seed1, Adam A. Arthurs

1, and Philip J. Millar

1,2

1Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario,

Canada; 2

Toronto General Research Institute, Toronto General Hospital, Toronto, Ontario,

Canada

Address for Correspondence and requests for reprints:

Philip J. Millar, PhD

ANNU 348A, 50 Stone Road East, Guelph, Ontario, Canada, N1G2W1

Telephone: 519-824-4120 x54818

Email: [email protected]

This research was supported by a Natural Science and Engineering Research Council of Canada (NSERC)

Discovery Grant (P.J.M. #06019), the Canada Foundation for Innovation (P.J.M. #34379), and the

Ontario Ministry of Research, Innovation, and Science (P.J.M. #34379). An Ontario Graduate

Scholarship (OGS) supported J.B.L. A Queen Elizabeth II Graduate Scholarship in Science and

Technology supported A.V.I. The authors declare no conflicts of interest relevant to the content of this

study. The authors declare that the results of the study are presented clearly, honestly, and without

fabrication, falsification, or inappropriate data manipulation and do not constitute endorsement by the

American College of Sports Medicine.

Medicine & Science in Sports & Exercise, Publish Ahead of Print DOI: 10.1249/MSS.0000000000001485

Copyright © 2017 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.

Abstract

Purpose: Whether differences in absolute muscle strength impact blood pressure (BP) responses

to relative intensity static exercise remains controversial but could contribute to known sex-based

differences and influence the interpretation of cross-sectional data. Methods: One hundred

thirty-two healthy participants (66 men and 66 women, age: 22±3yrs) underwent continuous

seated measurements of BP (Finometer) and heart rate (electrocardiography) during baseline rest

and two minutes of static handgrip (30% maximal voluntary contraction [MVC]). BP and heart

rate responses were quantified in 30-second epochs during exercise and compared between men

and women with and without statistical adjustment (ANCOVA) for differences in baseline BP

(or heart rate), forearm girth, and handgrip MVC. Within each sex, BP and heart rate responses

were compared also between tertiles of handgrip MVC (n=22 per group). Results: Men had

larger systolic, diastolic, and mean arterial pressure responses during static handgrip than women

(interaction term, All P<0.0005), though heart rates responses were similar (interaction term,

P=0.25). These sex-based BP differences persisted following statistical adjustment for

differences in baseline BP or forearm girth, however, controlling for handgrip MVC abolished

differences in BP responses during static handgrip exercise between men and women (interaction

term, All P>0.35). In men, BP responses were smaller within the lowest tertile of handgrip MVC

(interaction term, All P<0.006), while in women, BP responses were larger within the highest

tertile of handgrip MVC (interaction term, All P<0.04). Conclusion: Our findings suggest an

important between- and within-sex role of absolute handgrip strength in mediating the BP

response to static handgrip exercise and highlight the importance of controlling for inter-

individual differences in future work.

Key Words: Hemodynamic; Sex differences; Maximal voluntary contraction; Muscle mass;

Exercise


Introduction

Exercise is considered a valuable, non-invasive perturbation to uncover physiologically-

relevant differences in cardiovascular or autonomic function between groups that are not

apparent at rest (1,2). One of the most studied exercise modes involves submaximal static

handgrip contractions (i.e. 20-50% of maximal volitional contraction [MVC]) completed for a set

duration (e.g. 1 to 3 minutes) (3–10) or until failure (11–19). Static exercise produces

reproducible increases in heart rate and blood pressure (BP) through cardiac parasympathetic

withdrawal and sympathetic activation (20,21), though large inter-individual variability in

pressor responses exist (9).

The magnitude of cardiovascular responses to static exercise are thought to be governed

primarily by both the relative intensity and duration of the contraction, independent of the

amount of contracting muscle mass or absolute tension generated (22). However, the latter

assertions remain controversial as numerous small-scale studies have reported differences in BP

responses during similar relative intensity static handgrip and leg exercise (i.e. differences in

muscle mass) (23–25) or within participants when comparing the dominant to the non-dominant

leg with different absolute strength (24). Sex-based differences in absolute muscle strength (26)

parallel also observations that men demonstrate larger BP responses to fixed-duration (e.g. 2 - 3

minutes) 30% MVC static handgrip contractions than women (3–7). Unfortunately, prior studies

examining sex comparisons did not address specifically whether controlling for baseline

differences in muscle mass or strength ameliorated differences between men and women in

hemodynamic responses during static handgrip exercise. Additionally, men and women routinely

present with different resting BP values (15), which may impact responses due to regression to

the mean (27).


Supporting an important contribution of muscle strength in determining hemodynamic

responses to static handgrip exercise, inter-individual differences in relative force are negatively

correlated to static handgrip time-to-failure (12–14). As a result, even when completing a static

contraction at the same relative intensity those with higher target forces will fatigue earlier

causing intensity differences between participants during prolonged contractions. In prior work,

normalizing for static handgrip time-to-failure has abolished sex-based differences in BP

responses during 20-40% MVC static handgrip exercise in some (12,14,16,18,19) but not all

(11,13,15,17) studies. A major limitation of assessing static handgrip time-to-failure is that it can

be influenced by perception of effort through somatosensory, neurocognitive (e.g. learned

experience), psychological, and hedonistic (e.g. forearm discomfort/pain) inputs in order to reach

true physiological failure (28–30). Early termination of a contraction (due to disinterest or

discomfort) would confound normalization of BP and heart rate responses.

Therefore, the purpose of the study was to investigate, in a large cohort of 132 healthy

young men and women, potential sex differences in hemodynamic responses to 30% MVC static

handgrip exercise, with and without adjustment for differences in resting baseline BP, forearm

girth, and handgrip strength. To further probe the confounding role of handgrip strength, we

compared, within each sex, the hemodynamic responses to static handgrip exercise within tertiles

of handgrip MVC. We hypothesize that 1) males will have larger BP responses to static handgrip

than women but that these differences will be abolished following adjustment of baseline

covariates; and 2) within each sex, differences in BP responses will be detected across tertiles of

muscle strength.


Methods

Participants

One hundred thirty-two young healthy recreationally active men (n=66) and women

(n=66) were studied between January-August 2017 after providing informed written consent. All

of the women self-reported that they possessed a regular 28-day menstruation cycle and were

studied during the early follicular phase (between days 1-5). If women reported taking oral

contraception (n=29), they were studied similarly during the first five days of their placebo pills

to align with the early follicular phase. All participants where free of known cardiovascular or

metabolic disease and did not consume any chronic medications other than oral contraception.

The University of Guelph Research Ethics Board approved all procedures.

Experimental Protocol

Prior to the testing visit participants were asked to refrain from caffeine, alcohol, and

vigorous exercise for a minimum of 24 hours. Participants were studied for a single visit in a

light and temperature controlled laboratory. Following voiding and collection of anthropometric

measurements, participants were positioned upright on a comfortable chair with their feet up on

an ottoman for the duration of the study. To determine MVC, participants were asked to execute

two maximal handgrip contractions (Lafayette Instrument, Lafayette, LA) in their left hand. Nine

participants were left-handed (5 men; 4 women). Each contraction lasted ~3 seconds and was

separated by at least 30 seconds of rest. The highest value was taken as MVC. Forearm girth was

measured as the point of greatest circumference around the proximal quarter of the left forearm

using a measuring tape to the nearest tenth of a centimeter (31).


After instrumentation (~10 minutes), continuous measures of heart rate and BP, as well

as discrete minute-to-minute brachial BP were collected simultaneously over a five minute

resting baseline. Following the rest protocol, participants underwent continuous measurements of

heart rate and BP during a two minute baseline and two minute static handgrip contraction at

30% MVC.

Measurements

Single-lead electrocardiography (Lead II) was used to obtain beat-to-beat HR

(ADInstruments Pty Ltd, Australia). Discrete resting BP was measured from the left brachial

artery on a minute-to-minute basis using an automated sphygmomanometer (BPTru Medical

Devices, Coquitlam, Canada). Continuous beat-to-beat BP was recorded from the right middle

finger using photoelectric plethysmography (Finometer MIDI, Finapres Inc, Netherlands) to

monitor hemodynamic responses during static handgrip. All continuous data was digitized and

stored with LabChart (PowerLab, ADInstruments, Colorado Springs, CO) at a sampling

frequency of 1000 Hz.

Data and Statistical Analysis

Heart rate and BP measurements were averaged over the two minute baseline and in 30-

second epochs during static handgrip exercise; the changes from baseline were used for

statistical analyses. To examine the effects of handgrip strength on heart rate and BP responses

within men and women separately, each sex underwent division into tertiles (n=22 in each

group) based on handgrip MVC.


Statistical analyses were performed using IBM SPSS Statistics 24 (Armonk, NY) and

GraphPad Prism (GraphPad Software, La Jolla, CA). The Shapiro-Wilk test was used to assess

normality; only heart rate responses to static handgrip exercise were not normally distributed and

underwent mathematical transformation to achieve normality. Baseline characteristics between

men and women were assessed using unpaired two-tailed t-tests. Two-way mixed model

repeated measure analyses of variance (ANOVA) were used to evaluate the changes in

hemodynamic variables during static handgrip exercise both between sexes, and within male and

female tertiles separately. Similar two-way ANOVAs were used to compare directly heart rate

and BP responses between men and women matched for handgrip MVC. Significant main effects

and interactions were probed using Bonferroni post-hoc tests. To control for sex differences in

baseline BP (or heart rate), forearm girth, and/or handgrip MVC on heart rate and BP responses

to static handgrip exercise, data were analyzed using an analysis of covariance (ANCOVA). We

completed three ANCOVA models to test the effects of each covariate independently. Model one

was used to covariate baseline BP (or heart rate); model two to covariate forearm girth; and

model three to covariate handgrip MVC. Significance was considered P<0.05. Data presented as

mean ± SD, unless otherwise stated.

Results

Baseline participant characteristics comparing men and women are found in Table 1.

Participants were matched for age, body-mass index, diastolic BP, and mean arterial pressure

(All P>0.05), though height, body weight, handgrip MVC, and forearm girth were all larger in

men (All P<0.0001). Compared to women, men also had higher resting systolic BP (P=0.0009)

and lower resting heart rate (P<0.0001).


Effect of sex

Heart rate and BP increased during static handgrip exercise (time effect, all P<0.0001).

Systolic BP responses were different between men and women at 60 seconds (P=0.003), 90

seconds (P<0.0001), and 120 seconds (P<0.0001); diastolic BP responses were different at 90

seconds (P=0.0005) and 120 seconds (P=0.0001); and mean arterial pressure responses were

different at 60 seconds (P=0.04), 90 seconds (P=0.0001), and 120 seconds (P<0.0001). Heart

rate responses were not different between men and women (interaction term, P=0.25) (Figure 1).

Table 2 displays P-values for the main effect of sex and the interaction term after

adjusting for baseline differences in baseline BP (or heart rate), forearm girth, or handgrip MVC.

Statistical adjustment for baseline BP and forearm girth had no effect on the observed differences

in BP responses between men and women. In contrast, adjustment for handgrip MVC abolished

all sex-based differences in BP responses. To confirm this observation, we matched the 12

weakest men and 12 strongest women (MVC: 37 ± 3 kg vs. women: 36 ± 2 kg, P=0.54) and

found no significant main effects of sex (All P>0.16) or sex*time interactions (All P>0.35) for

heart rate and BP responses to static handgrip exercise.

Across the entire cohort, handgrip MVC was positively associated with systolic BP

(r=0.42; P<0.0001), diastolic BP (r=0.37; P<0.0001), mean arterial pressure (r=0.40; P<0.0001),

and to a lesser extent heart rate (r=0.22; P=0.01).

Influence of handgrip MVC on static handgrip responses in men

In men, the mean handgrip MVC was 39 ± 4 kg (range: 32-43 kg) in the first tertile, 46 ±

2 kg (range: 43-49 kg) in the second tertile, and 58 ± 7 kg (range: 50-75 kg) in the third tertile.

Systolic BP responses were larger in tertile two and three compared to tertile one during 60

seconds (P=0.01 and P=0.005, respectively), 90 seconds (P=0.003 and P=0.001, respectively),


and 120 seconds (Both P<0.0001). Diastolic BP responses were higher in tertile two compared to

tertile one at 60 seconds (P=0.04), while both tertile two and three were greater than tertile one at

90 seconds (P=0.002 and P=0.006, respectively) and 120 seconds (Both P<0.0001). Mean

arterial pressure responses were higher in tertile two and three compared to tertile one at 60

seconds (P=0.01 and P=0.02, respectively), 90 seconds (Both P=0.001) and 120 seconds (Both

P<0.0001). Heart rate responses were also greater in tertile two and three at 90 seconds

compared to tertile one (Both P=0.02) and tertile three was greater than tertile one at 30 seconds

(P=0.02), at 60 seconds (P=0.03), and 120 seconds (P=0.01). There were no differences between

tertile two and three for any variable (Figure 2).

Influence of handgrip MVC on static handgrip responses in women

In women, the mean handgrip MVC was 21 ± 4 kg (range: 13-25 kg) in the first tertile,

27 ± 1 kg (range: 25-29 kg) in the second tertile, and 34 ± 3 kg (range: 29-41 kg) in the third

tertile. Systolic BP responses were greater in tertile three compared to tertile two during 60

seconds (P=0.001), and greater than both tertile one and two at 90 seconds (P=0.03 and

P<0.0001, respectively) and 120 seconds (P=0.001 and P<0.0001, respectively). Diastolic BP

responses were higher in tertile three compared to tertile two at 60 seconds (P=0.02) and 90

seconds (P=0.008) and greater than both tertile one and two at 120 seconds (P=0.02 and P=0.01,

respectively). Mean arterial pressure responses were higher in tertile three compared to tertile

one and two at 60 seconds (P=0.048 and P=0.005, respectively) and 120 seconds (P=0.002 and

P=0.003, respectively). Additionally, tertile three had a greater mean arterial pressure response

than tertile two at 90 seconds (P=0.0009). Heart rate was not different between any of the

tertiles. There were no differences between tertile one and two for any variable (Figure 3).


Discussion

The present study sought to examine the effect of sex on BP and heart rate responses to

static handgrip exercise with and without statistical adjustment for differences in baseline BP (or

heart rate), forearm girth, and handgrip MVC. In support of our hypothesis, men had greater BP

responses to static handgrip exercise than women, though no differences in heart rate responses

were observed. After controlling for differences in baseline BP or forearm girth, these sex-based

differences in BP responses persisted. However, following adjustment for differences in

handgrip MVC, the differences in BP responses between men and women were abolished. The

examination of a large data set also permitted a novel examination of the effect of handgrip

MVC on within-sex BP and heart rate responses. These results demonstrate that, in men, BP

responses were smaller within the lowest tertile of handgrip MVC compared to the two stronger

groups, while in women, BP responses were larger in the strongest tertile of handgrip MVC

compared to the two weaker groups. Overall, these results demonstrate the importance of

absolute muscle strength in determining the pressor response to static handgrip exercise and

emphasize the need to control for inter-individual differences.

Prior studies investigating the effect of sex on hemodynamic responses between men and

women during fixed-duration static handgrip exercise failed to account for differences in

baseline BP, muscle strength, or muscle mass, and in some cases restricted analysis to only mean

arterial pressure or failed to account for different phases of the menstrual cycle in women (3–7).

Each of these studies concluded that men demonstrate greater BP responses during static

handgrip compared to women. In an effort to control for confounding effects of muscle strength,

a number of studies have normalized data to account for differences in static handgrip time-to-

failure, which in some studies has eliminated these sex differences (12,14,16,18,19), though

inconsistently as others reported that larger BP responses in men persisted (11,13,15,17).


Additionally, in two studies, females did not possess longer static handgrip time-to-failure

responses, even though they had a lower absolute handgrip MVC than men (15,19). In one of

these studies men demonstrated a greater BP response (15), while the other study showed no BP

differences between men and women (19). This inconsistency in results, combined with time-to-

failure exercises not being comfortable and requiring great motivation to reach true fatigue (28),

potentially makes handgrip to fatigue a non-ideal measure for normalizing between groups.

The primary finding in the present study was that adjustment for handgrip MVC, but not

baseline BP or forearm girth, abolished sex-based differences in BP responses during a 30%

MVC 2-minute static handgrip contraction. This finding emphasizes the importance of absolute

strength on BP responses when performing a relative intensity fixed duration static handgrip

contraction between men and women. Moreover, a second novel finding was that within both

men and women, BP responses differed based on tertile groupings of handgrip MVC. This

finding further supports the notion that absolute strength can impact BP responses during static

handgrip. Interestingly, examination of the strength-based tertiles across the entire cohort

identified three distinct bands of BP responses. The first band consisting of the two weakest

female tertiles, the second consisting of the strongest females and weakest males, and the third

consisting of the two strongest male tertiles. The present study did not investigate the

mechanism(s) responsible for the confounding effects of handgrip MVC on BP responses,

however, we speculate that differences in skeletal muscle fibre type distribution may be

involved. In support of this hypothesis, a higher proportion of fast-twitch brachioradialis muscle

fibres was correlated positively with mean arterial pressure responses (r=0.89) at the end of a two

minute 40% MVC static handgrip contraction (32). Similarly, the diastolic blood pressure

response to two minutes of electrically-evoked static plantar flexion at 30% MVC was related to

fast isomyosin content of the lateral gastrocnemius and soleus (33). Fast-twitch muscle fibres


have been associated with higher rates of metabolite production during static exercise (32,34),

which would stimulate metabolically-sensitive group III/IV skeletal muscle afferents (32,35) that

relay peripheral afferent feedback to increase central sympathetic outflow and ultimately BP

(20,21).

The present findings have important implications for the interpretation of past and future

studies, demonstrating a critical need to control for muscle strength when performing cross-

sectional designs with between-group differences in handgrip MVC. Studies drawing

conclusions from groups with different handgrip MVC may show attenuated hemodynamic

responses or underestimate a true difference in responses between groups. For example,

attenuated BP responses during a two minute static handgrip at 30% MVC were reported in

individuals with down syndrome, although this group had lower absolute handgrip MVC (11.6 ±

1.6 kg) compared to the control group (27.4 ± 2.8 kg) without down syndrome (10). Whether a

true physiological attenuation in BP responses exists may be confounded by the difference in

absolute strength between the two groups. In contrast, Sterns et al. reported no differences in BP

responses during two minutes of static handgrip at 30% MVC between patients with heart failure

and a healthy control group (8). The heart failure group again had weaker absolute handgrip

MVC (38 ± 3 kg) compared to the healthy controls (45 ± 2 kg). This difference in absolute

strength may ultimately underestimate the true difference in BP responses between these two

groups. Therefore, based on the findings from the present study, controlling for differences in

absolute handgrip MVC are essential when comparing between participants.

We acknowledge several limitations in the present study. We studied only young healthy

males and females, which may limit the generalizability to older or diseased cohorts. Similarly,

whether BP responses to larger muscle mass exercise exhibit the same patterns as small muscle

mass handgrip exercise warrants further work. The specific duration and intensity may also

impact the observed findings. We selected the two minute, 30% MVC static handgrip contraction


as it represents one of the most commonly used exercise modes in the literature (3,4,6,8,10),

however, whether similar findings are present with alternative protocols is unclear. Future

studies are required to test BP responses to a variety of relative and absolute intensities to

confirm these results. We also acknowledge that circumferential measurements of forearm girth

provide an indirect estimate of muscle mass (36). Finally, using handgrip MVC to determine

each individual’s relative exercise intensity may not be the best indicator of underlying

metabolic activity (37) and future studies should consider the use of forearm critical force.

Nevertheless, the present results demonstrate that the use of already collected MVC data may

suffice in controlling for inter-individual differences in handgrip strength.

In conclusion, our results demonstrate that the larger BP responses to static handgrip

exercise observed consistently in men compared to women are abolished after adjustment for

handgrip MVC but not baseline BP or forearm girth. Further, we show that differences in

handgrip MVC also are associated with variability in BP responses within both men and women

separately. These findings underscore the importance of controlling for inter-individual

differences in absolute muscle strength when examining cardiovascular responses to exercise.

Acknowledgements

This research was supported by a Natural Science and Engineering Research Council of Canada

(NSERC) Discovery Grant (P.J.M. #06019), the Canada Foundation for Innovation (P.J.M.

#34379), and the Ontario Ministry of Research, Innovation, and Science (P.J.M. #34379). An

Ontario Graduate Scholarship (OGS) supported J.B.L. A Queen Elizabeth II Graduate

Scholarship in Science and Technology supported A.V.I. The authors declare no conflicts of

interest relevant to the content of this study. The authors declare that the results of the study are

presented clearly, honestly, and without fabrication, falsification, or inappropriate data

manipulation and do not constitute endorsement by the American College of Sports Medicine.


References

1. Freeman R. Assessment of cardiovascular autonomic function. Clin Neurophysiol.

2006;117(4):716–30.

2. Khurana RK, Setty A. The value of the isometric hand-grip test--studies in various

autonomic disorders. Clin Auton Res. 1996;6(4):211–8.

3. Ettinger SM, Silber DH, Collins BG, et al. Influences of gender on sympathetic nerve

responses to static exercise. J Appl Physiol. 1996;80(1):245–51.

4. Hogarth AJ, Mackintosh AF, Mary DASG. Gender-related differences in the sympathetic

vasoconstrictor drive of normal subjects. Clin Sci. 2007;112(6):353–61.

5. Matthews KA, Stoney CM. Influences of sex and age on cardiovascular responses during

stress. Psychosom Med. 1988;50(1):46–56.

6. McAdoo WG, Weinberger MH, Miller JZ, Fineberg NS, Grim CE. Race and gender

influence hemodynamic responses to psychological and physical stimuli. J Hypertens.

1990;8(10):961–7.

7. Simoes GMS, Campagnaro BP, Tonini CL, Meyrelles SS, Kuniyoshi FHS, Vasquez EC.

Hemodynamic reactivity to laboratory stressors in healthy subjects: influence of gender and

family history of cardiovascular diseases. Int J Med Sci. 2013;10(7):848–56.

8. Sterns DA, Ettinger SM, Gray KS, et al. Skeletal muscle metaboreceptor exercise responses

are attenuated in heart failure. Circulation. 1991;84(5):2034–9.

9. Watanabe K, Ichinose M, Tahara R, Nishiyasu T. Individual differences in cardiac and

vascular components of the pressor response to isometric handgrip exercise in humans. Am

J Physiol Heart Circ Physiol. 2014;306(2):H251-260.


10. Heffernan KS, Baynard T, Goulopoulou S, et al. Baroreflex sensitivity during static exercise

in individuals with Down Syndrome. Med Sci Sports Exerc. 2005;37(12):2026–31.

11. Ewing DJ, Irving JB, Kerr F, Wildsmith JA, Clarke BF. Cardiovascular responses to

sustained handgrip in normal subjects and in patients with diabetes mellitus: a test of

autonomic function. Clin Sci Mol Med. 1974;46(3):295–306.

12. Hunter SK, Critchlow A, Shin I-S, Enoka RM. Fatigability of the elbow flexor muscles for a

sustained submaximal contraction is similar in men and women matched for strength. J

Appl Physiol. 2004;96(1):195–202.

13. Hunter SK, Enoka RM. Sex differences in the fatigability of arm muscles depends on

absolute force during isometric contractions. J Appl Physiol. 2001;91(6):2686–94.

14. Hunter SK, Schletty JM, Schlachter KM, Griffith EE, Polichnowski AJ, Ng AV. Active

hyperemia and vascular conductance differ between men and women for an isometric

fatiguing contraction. J Appl Physiol. 2006;101(1):140–50.

15. Jarvis SS, VanGundy TB, Galbreath MM, et al. Sex differences in the modulation of

vasomotor sympathetic outflow during static handgrip exercise in healthy young humans.

Am J Physiol Regul Integr Comp Physiol. 2011;301(1):R193-200.

16. Jones PP, Spraul M, Matt KS, Seals DR, Skinner JS, Ravussin E. Gender does not influence

sympathetic neural reactivity to stress in healthy humans. Am J Physiol Heart Circ Physiol.

1996;270(1):H350–7.

17. Momen A, Handly B, Kunselman A, Leuenberger UA, Sinoway LI. Influence of sex and

active muscle mass on renal vascular responses during static exercise. Am J Physiol Heart

Circ Physiol. 2006;291(1):H121-126.

18. Petrofsky JS, Burse RL, Lind AR. Comparison of physiological responses of women and

men to isometric exercise. J Appl Physiol. 1975;38(5):863–8.


19. Sanchez J, Pequignot JM, Peyrin L, Monod H. Sex differences in the sympatho-adrenal

response to isometric exercise. Eur J Appl Physiol. 1980;45(2–3):147–54.

20. Lind AR, Taylor SH, Humphreys PW, Kennelly BM, Donald KW. The circulatory effects of

sustained voluntary muscle contraction. Clin Sci. 1964;27:229–44.

21. Seals DR, Chase PB, Taylor JA. Autonomic mediation of the pressor responses to isometric

exercise in humans. J Appl Physiol. 1988;64(5):2190–6.

22. Lind AR, McNicol GW. Circulatory responses to sustained hand-grip contractions performed

during other exercise, both rhythmic and static. J Physiol. 1967;192(3):595–607.

23. Mitchell JH, Payne FC, Saltin B, Schibye B. The role of muscle mass in the cardiovascular

response to static contractions. J Physiol. 1980;309:45–54.

24. Mitchell JH, Schibye B, Payne FC, Saltin B. Response of arterial blood pressure to static

exercise in relation to muscle mass, force development, and electromyographic activity.

Circ Res. 1981;48(6 Pt 2):I70-75.

25. Seals DR, Washburn RA, Hanson PG, Painter PL, Nagle FJ. Increased cardiovascular

response to static contraction of larger muscle groups. J Appl Physiol. 1983;54(2):434–7.

26. Leyk D, Gorges W, Ridder D, et al. Hand-grip strength of young men, women and highly

trained female athletes. Eur J Appl Physiol. 2007;99(4):415–21.

27. Bland JM, Altman DG. Regression towards the mean. BMJ. 1994 Jun 4;308(6942):1499.

28. Bowie W, Cumming GR. Sustained handgrip-reproducibility: effects of hypoxia. Med Sci

Sports Exerc. 1971;3(1):24–31.

29. Nobrega ACL, O’Leary D, Silva BM, Marongiu E, Piepoli MF, Crisafulli A. Neural

regulation of cardiovascular response to exercise: role of central command and peripheral

afferents. BioMed Res Int. 2014;2014:478965.


30. Williamson JW. The relevance of central command for the neural cardiovascular control of

exercise. Exp Physiol. 2010;95(11):1043–8.

31. Hogrel J-Y. Grip strength measured by high precision dynamometry in healthy subjects from

5 to 80 years. BMC Musculoskelet Disord. 2015;16:139.

32. Sadamoto T, Mutoh Y, Miyashita M. Cardiovascular reflexes during sustained handgrip

exercise: role of muscle fibre composition, potassium and lactate. Eur J Appl Physiol.

1992;65(4):324–30.

33. Carrington CA, White MJ, Harridge SD, Goodman M, Cummins P. The relationship between

the pressor response to involuntary isometric exercise and the contractile protein profile of

the active muscle in man. Eur J Appl Physiol. 1995;72(1–2):81–5.

34. Saito M. Differences in muscle sympathetic nerve response to isometric exercise in different

muscle groups. Eur J Appl Physiol. 1995;70(1):26–35.

35. McCord JL, Kaufman MP. Reflex Autonomic Responses Evoked by Group III and IV

Muscle Afferents. In: Kruger L, Light AR, editors. Translational Pain Research: From

Mouse to Man. Boca Raton, FL: CRC Press/Taylor & Francis; 2010. p. 283-300.

36. Fuller NJ, Laskey MA, Elia M. Assessment of the composition of major body regions by

dual-energy X-ray absorptiometry (DEXA), with special reference to limb muscle mass.

Clin Physiol. 1992;12(3):253–66.

37. Kellawan JM, Tschakovsky ME. The single-bout forearm critical force test: a new method to

establish forearm aerobic metabolic exercise intensity and capacity. PloS One.

2014;9(4):e93481.


Figure Legends

Figure 1. Systolic blood pressure (A), diastolic blood pressure (B), mean arterial pressure (C), and

heart rate (D) responses during 2 minutes of 30% MVC static handgrip in men (n=66) and women

(n=66); *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001 vs. women. Mean ± SEM.


heart rate (D) responses during 2 minutes of 30% MVC static handgrip in men (n=66) divided by

tertiles of handgrip MVC (n=22 in each group). *, P<0.05; **, P<0.01; ***, P<0.001; ****,

P<0.0001 vs. tertile 2. †, P<0.05; ††, P<0.01; †††, P<0.001; ††††, P<0.0001 vs. tertile 3. Mean ±

SEM.


heart rate (D) responses during 2 minutes of 30% MVC static handgrip in women (n=66) divided by

tertiles of handgrip MVC (n=22 in each group). *, P <0.05; **, P <0.01; ***, P <0.001; ****, P

<0.0001 vs. tertile 1. †, P <0.05; ††, P <0.01; †††, P <0.001; ††††, P <0.0001 vs. tertile 2. Mean ±

SEM.


Table 1. Resting baseline characteristics in men and women.

Characteristic Men (n=66) Women (n=66)

Age (years) 22 ± 3 [18 – 30] 21 ± 2 [18 – 29]

Height (cm) 178 ± 7 [163 – 196] 165 ± 7 [147 – 182]****

Weight (kg) 77 ± 13 [52 – 124] 63 ± 9 [44 – 86]****

Body mass index (kg/m2) 24 ± 3 [18 – 35] 23 ± 3 [17 – 33]

Heart rate (bpm) 63 ± 10 [44 – 92] 71 ± 12 [52 – 101]****

Systolic blood pressure (mmHg) 107 ± 8 [91 – 133] 102 ± 9 [83 – 123]***

Diastolic blood pressure (mmHg) 64 ± 7 [50 – 79] 66 ± 8 [51 – 87]

Mean arterial pressure (mmHg) 79 ± 7 [64 – 97] 78 ± 8 [62 – 99]

Maximal volitional contraction (kg) 48 ± 9 [32 – 75] 27 ± 6 [13 – 41]****

Forearm circumference (cm) 27 ± 2 [22 – 31] 23 ± 2 [19 – 27]****

Mean ± SD [Range]. *, P<0.05; **, P<0.01; ***, P<0.001; ****, P<0.0001 vs. men.


Table 2. P-values of unadjusted and adjusted models for sex (group) and sex*time (interaction)

effects.

Variable Unadjusted Model 1

Model 2 Model 3

Sex Sex*Time Sex Sex*Time Sex

Sex*Time Sex Sex*Time

Systolic blood pressure <0.0001 <0.0001 <0.0001 <0.0001 0.03

0.01 0.68 0.59

Diastolic blood pressure 0.001 0.0005 0.002 0.001 0.03

0.03 0.43 0.35

Mean arterial pressure 0.0003 <0.0001 0.0003 <0.0001 0.03

0.01 0.47 0.50

Heart rate 0.53 0.25 0.78 0.25 0.74

0.29 0.04 0.07

Model 1 covariates baseline blood pressure or heart rate; Model 2 covariates forearm girth;

Model 3 covariates handgrip maximal volitional contraction.


muscle strength influences pressor responses to static

Documents