sex differences in cardiac baroreflex sensitivity ... · and women (16, 17). in particular, women...

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. . . 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 Sex Differences in Cardiac Baroreflex Sensitivity following Isometric Handgrip Exercise André L. Teixeira 1 , Raphael Ritti-Dias 2 , Diego Antonino 1 , Martim Bottaro 1 , Philip J. Millar 3 , and Lauro C. Vianna 1 1 NeuroVASQ Integrative Physiology Laboratory, Faculty of Physical Education, University of Brasília, Brasília, DF, Brazil; 2 Department of Physical Education, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil; 3 Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada Accepted for Publication: 6 November 2017

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Page 1: Sex Differences in Cardiac Baroreflex Sensitivity ... · and women (16, 17). In particular, women present commonly with reduced cardiac baroreflex sensitivity (cBRS), a measure of

. . . 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

Sex Differences in Cardiac Baroreflex Sensitivity following

Isometric Handgrip Exercise

André L. Teixeira

1, Raphael Ritti-Dias

2, Diego Antonino

1, Martim Bottaro

1,

Philip J. Millar3, and Lauro C. Vianna

1

1NeuroVASQ – Integrative Physiology Laboratory, Faculty of Physical Education, University of

Brasília, Brasília, DF, Brazil; 2Department of Physical Education, Hospital Israelita Albert

Einstein, São Paulo, SP, Brazil; 3

Department of Human Health and Nutritional Sciences,

University of Guelph, Guelph, Ontario, Canada

Accepted for Publication: 6 November 2017

Page 2: Sex Differences in Cardiac Baroreflex Sensitivity ... · and women (16, 17). In particular, women present commonly with reduced cardiac baroreflex sensitivity (cBRS), a measure of

Sex Differences in Cardiac Baroreflex Sensitivity following Isometric

Handgrip Exercise

André L. Teixeira1, Raphael Ritti-Dias

2, Diego Antonino

1, Martim Bottaro

1,

Philip J. Millar3, and Lauro C. Vianna

1

1NeuroVASQ – Integrative Physiology Laboratory, Faculty of Physical Education, University of

Brasília, Brasília, DF, Brazil; 2

Department of Physical Education, Hospital Israelita Albert

Einstein, São Paulo, SP, Brazil; 3

Department of Human Health and Nutritional Sciences,

University of Guelph, Guelph, Ontario, Canada

Correspondence:

Lauro C. Vianna, PhD

NeuroVASQ - Integrative Physiology Laboratory

Faculty of Physical Education University of Brasília

Darcy Ribeiro Campus, Brasília, Brazil

tel: +55 (61) 31072531

fax: +55 (61) 31072512

email: [email protected]

This study was in part funded by CAPES, CNPq, and FAPDF. The results of this study are

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

manipulation and the results of the present study do not constitute endorsement by ACSM. The

authors declare that they have no conflict of interest.

Medicine & Science in Sports & Exercise, Publish Ahead of Print DOI: 10.1249/MSS.0000000000001487

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

Page 3: Sex Differences in Cardiac Baroreflex Sensitivity ... · and women (16, 17). In particular, women present commonly with reduced cardiac baroreflex sensitivity (cBRS), a measure of

ABSTRACT

Purpose: To investigate potential sex-related differences on spontaneous cardiac baroreflex

sensitivity (cBRS) following acute isometric handgrip (IHG) exercise. Methods: Twenty men

(23±3 years) and 20 women (24±4 years) randomly performed four sets of 2-min IHG exercise

(two sets for each limb) at 30% maximum voluntary contraction (MVC – experimental) or 3%

MVC (sham). Beat-to-beat heart rate (HR) and arterial blood pressure (BP) were monitored

using finger photoplethysmography before and 10-, 20-, and 30-min following IHG.

Spontaneous cBRS was assessed via the sequence technique and cardiac autonomic modulation

via time- and frequency-domain HR variability. Results: Following IHG, spontaneous cBRS

increased during 10-min of recovery in men (∆13±5%, P=0.03 vs. rest) and increased further in

women (∆23±4%, P<0.01 vs. rest; P=0.04 vs. men). During 20 and 30-min of recovery, cBRS

returned to baseline in men, but remained elevated in women. HR decreased 10-min following

IHG in men (10-min: ∆-2±1 beats.min-1

, P<0.01 vs. rest; 20-min: ∆-1±1 beats.min-1

, P=0.39 vs.

rest; 30-min: ∆1±1 beats.min-1

, P=0.31 vs. rest) and throughout recovery in women (10-min: ∆-

5±1 beats.min-1

, P<0.01 vs. rest; 20-min: ∆-3±1 beats.min-1

, P<0.01 vs. rest; 30-min: ∆-2±1

beats.min-1

, P<0.01 vs. rest). Systolic BP increased 10-min after IHG and remained elevated

during 20-min and 30-min in men (P<0.05). In women, systolic BP increased during 10-min

(P<0.01) and returned to baseline during 20-min and 30-min of recovery. Time domain HR

variability (root mean square of successive differences) was increased during recovery in men

and women (P<0.05). Sham had no effect on any variables. Conclusion: Acute IHG exercise

increases cBRS and cardiac vagal activity in healthy young subjects, but the magnitude and the

time course of changes in cBRS differ between men and women.

Key Words: static exercise, autonomic nervous system, heart rate, blood pressure.

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

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INTRODUCTION

Isometric handgrip (IHG) training (>4 weeks) has been shown to reduce resting arterial

blood pressure (BP) in both normotensive and hypertensive populations with a magnitude of

effect larger than that reported previously with dynamic aerobic or resistance training (1-5).

Given this accumulating body of evidence, the American Heart Association indicates that IHG

training may be used as a potential alternative strategy to lower resting BP (Class IIB, Level of

Evidence C) (6). However, the mechanisms underlying these chronic adaptations remain largely

unknown, although improvements in cardiac autonomic modulation have been reported (7, 8).

Despite the potential benefits of IHG for BP management, relatively few studies have

assessed the acute effects of IHG on BP control (9-12). This area of study could yield important

mechanistic information given that chronic adaptations may result from temporal summation of

acute responses (13). A single bout of IHG exercise, consisting of four 2-minute isometric

contractions at 30% of maximal voluntary effort, decreased systolic BP and improved cardiac

parasympathetic modulation in older (primarily male) normotensive subjects (10, 11). The latter

observation suggests involvement of the autonomic nervous system but provides little insight

into potential mechanisms. More recently, an acute bout of bilateral isometric leg exercise was

reported similarly to lower BP and increase cardiac parasympathetic modulating in concert with

increased sensitivity of arterial baroreflex control of heart rate (HR) in pre-hypertensive men

(12).

The arterial baroreflex represents an important closed-loop, negative feedback control

system involved in regulating BP (14). Mechanically-sensitive receptors located in the carotid

body and aortic arch relay information to the brainstem regarding beat-to-beat changes in blood

pressure (14). The resultant neural feedback provides critical information to modulate HR

(cardiac baroreflex) or peripheral vasoconstrictor outflow (sympathetic baroreflex) in order to

maintain pressure homeostasis at rest and in response to pertubations (e.g. standing) (15).

Importantly, it is now well established that the mechanisms regulating BP differ between men

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

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and women (16, 17). In particular, women present commonly with reduced cardiac baroreflex

sensitivity (cBRS), a measure of reflexive vagal modulation (18-20). Such sex-based differences

in BP control may contribute to a recent meta-analytic observation that men experience larger

reductions in BP following IHG training compared to women (4). However, recent trials not

included in this analysis suggests that potential sex differences are unclear, Badrov et al. (21) and

Somani et al. (22) demonstrated that IHG training lowered similarly arterial BP in healthy men

and women. Unfortunately, prior studies examining the acute cardiovascular effects of IHG have

recruited predominantly (or solely) men and were not designed to investigate potential sex-

related differences in the BP control.

Therefore, the present study was undertaken to test the hypothesis that a single bout of

IHG exercise would improve BP control by increasing cBRS and cardiac parasympathetic

modulation in young healthy subjects, and to characterize the potential sex differences in these

responses.

METHODS

Participants

Twenty men (mean ± standard deviation, 23 ± 3 years) and 20 women (24 ± 4 years)

participated in the study. All subjects were healthy, normotensive, non-smokers, and were

recreationally active (self-reported habitual physical activity for at least 6 consecutive months

with a minimum frequency of 3 days per week in ≥ 30-min sessions). Subjects had no history or

symptoms of cardiovascular, pulmonary, metabolic, or neurological disease as determined from a

detailed medical health history questionnaire. No subjects were using prescribed or over-the-

counter medications. To avoid potential influence of female sex hormones on BP control, all

women were non-users of oral contraceptive pills for at least six consecutive months and were

studied during the early follicular phase of their menstrual cycle (i.e. first five days after

menstruation onset). Participants were recruited through posters placed at the University of

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

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Brasília, Brazil. Informed written consent was obtained from all subjects and all procedures were

approved by the University of Brasília institutional research committee in accordance with the

Declaration of Helsinki (CAAE: 38922414.7.0000.0030).

Experimental protocol

The study involved a prospective randomized, sham-controlled, cross-over design,

whereby each subject completed both experimental and sham interventions separated by 48–72

h. All subjects were asked to refrain from consuming caffeine/alcohol and from engaging in

physical exercise for 6 and 24 h, respectively, prior to the tests. Subjects were 2-h postprandial

upon arrival to the laboratory. To avoid potential diurnal variations, subjects were always tested

at the same time of day for each subject and in the same quiet, temperature-controlled room (22–

24°C).

Upon entering the laboratory, weight and height were determined via standard methods,

and body mass index (BMI) calculated. Following instrumentation, the subjects were asked to be

seated (90° of hip and knee flexion) and rest for 20 min. The initial 10-min rest period was used

for stabilization of cardiovascular variables, while the final 10-min period was used to collect

baseline measurements. A handgrip dynamometer was interfaced with a personal computer so

that real-time force output feedback could be displayed visually to the subjects (Powerlab 16/35,

AD instruments, Australia). Subjects completed three maximum isometric voluntary contractions

(MVC), each separated by >1 min of rest, in each limb. The highest of three maximal efforts was

designated MVC. Subjects next performed four sets of unilateral IHG (two for each limb). The

protocol consisted of 2-min static contractions at 30% (experimental) or 3% (sham) MVC

separated by 1-min rest periods (11). Following completion of IHG, seated recovery was

monitored for 30 min.

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

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Continuous beat-to-beat HR and arterial BP were measured using finger

photoplethysmography (Human NIBP Controller, AD instruments, NSW, Australia). Brachial

arterial BP was also measured with an automated digital sphygmomanometer (Dixtal, DX2022,

Brazil) for absolute measures of BP and to confirm finger measurement accuracy. Respiratory

movements were monitored using a strain-gauge pneumograph placed in a stable position around

the abdomen (Pneumotrace; UFI, Morro Bay, CA) in order to avoid the potential confounding

influence of large respiratory excursions on cardiovascular measurements and to ensure subjects

did not perform any Valsalva maneuvers during IHG. Measurements were performed during

baseline (10-min) and thrice following IHG (5th

to 10th

min, 15th

to 20th

min and 25th

to 30th

min

of recovery). Rating of perceived exertion (RPE) was obtained at the end of exercise using the

OMNI-RES scale (0–10) (23).

Spontaneous cBRS

Spontaneous cBRS was assessed using the sequence technique as previously reported

(24, 25). The sequence technique is based on the identification of consecutive beats in which

progressive increases (or decreases) in systolic BP (input variable) are followed by a progressive

lengthening (or shortening) in RR interval (output variable). Briefly, sequences of three or more

consecutive and concurrent beats with corresponding increases or decreases in systolic BP and

RR interval were identified as arterial baroreflex sequences (CardioSeries v2.4, Brazil).

Sequences of ≥ 3 consecutive cardiac cycles were detected only when the variations in systolic

BP and RR interval were ≥ 1 mmHg and ≥ 1.0 ms, respectively. A linear regression was applied

to each individual sequence and only those sequences in which r was >0.85 were accepted. The

slopes of the systolic BP and RR interval relationships for up and down sequences were then

calculated and averaged for a measure of spontaneous cBRS. Overall results were similar when

HR was used as the dependent variable for these cBRS measures and therefore only RR interval

measures are presented.

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

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HR variability

HR variability was determined in accordance with the guidelines of the Task Force of

the European Society of Cardiology and the North American Society of Pacing and

Electrophysiology (26). Variables were sampled at 1000 Hz and stored for offline analysis

(CardioSeries v2.4, Brazil). Only segments without signal noise were analyzed. All ectopic beats

on the ECG trace were identified both automatically and manually before exclusion from the

analysis. Time domain HR variability was performed using the square root of the mean of the

sum of successive differences in RR interval (RMSSD) as recommended for the estimation of

short-term high-frequency variability of HR that is primarily mediated by parasympathetic nerve

activity (26). A fast Fourier transformation (512 points) was used for spectral analysis of HRV.

The power spectra were quantified by measuring the area under the following frequency bands:

very low frequency power (VLF) (<0.04Hz), low-frequency power (LF) (0.04–0.15 Hz) and

high-frequency power (HF) (0.15–0.4 Hz). Normalized units were calculated by dividing each

spectral band by the total power minus the VLF power and were multiplied by 100. The ratio of

LF to HF power (LF/HF) was also calculated as a measure of cardiac autonomic balance (26).

Statistical analyses

An a priori sample size calculation was completed for the primary variable, cBRS gain

(G*Power 3.1 Dusseldorf University, Germany), based on a mean difference of 33 ± 1% in

cBRS gain between men and women (18, 19) with an α = 0.05 and power of 0.80. The resultant

calculation yielded an estimated sample size of 10 subjects in each group. Comparisons of

physiological variables were made using three-way analyses of variance (ANOVA) with

repeated measures, in which sex (men, women), time [baseline, recovery (10-min, 20-min, 30-

min)], and trial (experimental, sham) were the main factors. Comparisons of changes (∆) during

experimental protocol were made using a 2 x 3 (sex x time) ANOVA. In addition, an ANCOVA

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

Page 9: Sex Differences in Cardiac Baroreflex Sensitivity ... · and women (16, 17). In particular, women present commonly with reduced cardiac baroreflex sensitivity (cBRS), a measure of

(with baseline score as a covariate) analysis were performed to compare relative changes from

rest in physiological variables throughout recovery between men and women. Post hoc analysis

was employed using LSD test to investigate main effects and interactions. Baseline

characteristics were compared using an independent sample t test. Statistical significance was set

at P < 0.05 and values are presented as means ± S.E.M. Analyses were conducted using

Statistical Package for the Social Sciences (SPSS, version 22, USA) for windows.

RESULTS

Subject baseline characteristics are displayed in Table 1. Men and women were matched

for age, however, women had lower body weight, height, and BMI compared with men (All P <

0.01). In addition, measures of right and left handgrip MVC (absolute and relative to body

weight) were lower in women (All P < 0.01). Importantly, RPE was not different between groups

during both sham (men: 1.0 ± 0.3 vs. women: 1.5 ± 0.3; P = 0.16) and experimental (men: 8.5 ±

0.3 vs. women: 8.9 ± 0.2; P = 0.23) sessions.

Hemodynamics variables are shown in Table 2. At rest, HR was higher (P < 0.01)

whereas arterial BP was lower (P < 0.01) in women than men. In men, HR decreased slightly

from rest during 10-min of recovery in the experimental protocol (∆-2 ± 1 beats.min-1

; P < 0.01

vs. rest) and returned to baseline during 20-min (∆-1 ± 1 beats.min-1

; P = 0.39 vs. rest) and 30-

min (∆1 ± 1 beats.min-1

; P = 0.31 vs. rest) of recovery. In women, HR remained lower from rest

during the recovery period (10-min: ∆-5 ± 1 beats.min-1

, P < 0.01 vs. rest; 20-min: ∆-3 ± 1

beats.min-1

, P < 0.01 vs. rest; 30-min: ∆-2 ± 1 beats.min-1

, P < 0.01 vs. rest). Systolic BP

increased from rest following 10-min of IHG (∆6 ± 1 mm Hg, P < 0.01 vs. rest) and remained

slightly elevated during 20-min (∆2 ± 1 mm Hg, P = 0.02 vs. rest) and 30-min (∆2 ± 1 mm Hg, P

= 0.02 vs. rest) in men. In women, systolic BP increased from rest during 10-min (∆3 ± 1 mm

Hg, P < 0.01 vs. rest) and returned to baseline during 20-min (∆1 ± 1 mm Hg, P = 0.15 vs. rest)

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

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and 30-min (∆1 ± 1 mm Hg, P = 0.22 vs. rest) of recovery. No interaction effects were found for

diastolic or mean BP, though both had sex and time effects (Table 2). During the sham protocol,

all hemodynamics variables remained unchanged from rest in both men and women. Similarly,

respiratory rate were not different between men and women during both experimental and sham

protocols (P > 0.05; data not shown).

No interaction effects were found for any measure of HR variability (All P > 0.05), but

all presented significant time effects (Table 2). Following IHG, total power and RMSSD

increased from rest in the experimental protocol in both men and women (Table 2).

Figure 1 shows cBRS gain at rest and following IHG at 30% MVC (experimental) and

3% MVC (sham) in both men (panel A) and women (panel B). As expected, resting cBRS gain

was higher in men compared with women (P = 0.01). During 10-min of recovery in the

experimental protocol, cBRS increased from rest in both men and women. However, during 20-

min cBRS returned to baseline in men and remained elevated in women. cBRS was unchanged in

both men and women throughout the sham protocol (P > 0.05). The percent change (∆) in cBRS

from rest to recovery intervals are presented in Figure 2. Following 10-min of IHG in the

experimental protocol, cBRS increased in men (∆13 ± 5%, P = 0.03 vs. rest) and further

increased in women (∆23 ± 4%, P < 0.01 vs. rest; P = 0.04 vs. men). During 20-min and 30-min

of recovery, cBRS returned to baseline in men (∆-4 ± 4%, P = 0.22 vs. rest and ∆-7 ± 4%, P <

0.12 vs. rest, respectively), but remained elevated in women during 20-min (∆14 ± 4%, P < 0.01

vs. rest; P < 0.01 vs. men) and slightly, but not significantly elevated during 30-min (∆7 ± 6%, P

= 0.17 vs. rest; P < 0.01 vs. men). Adjustment for baseline differences in HR did not alter the

interpretation of cBRS results.

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

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DISCUSSION

The novel main finding of the present study is that a single bout of IHG increases

acutely spontaneous cBRS gain in young healthy subjects; however, the magnitude and time

course of these responses differed between men and women. In men, cBRS increased during 10-

min of recovery and returned to baseline after 20-min of IHG, but in women, cBRS markedly

increased from rest during 10-min and remained elevated until 30-min of recovery. In addition,

acute IHG exercise was able to reduce HR and increase RMSSD, a non-invasive marker of

cardiac parasympathetic activity, in both men and women. Collectively, these findings suggest

that one session of IHG exercise can acutely increase the sensitivity of arterial baroreflex control

of HR, a measure of reflexive vagal modulations, though sex dependent differences in responses

are present.

Historically, fatiguing isometric efforts have been associated with exaggerated

hypertensive responses and contraindicated for special populations (27). However, low-to-

moderate intensity, submaximal, isometric contractions produce cardiovascular responses similar

to dynamic aerobic (12) and resistance exercise (28). Wiley et al. (29) first reported the

hypotensive effects of submaximal IHG exercise training, after which, a number of randomized

controlled and uncontrolled trials have investigated a role for isometric exercise training to

reduce BP. Recent meta-analyses have confirmed reductions in BP, which may also be greater

following isometric training when compared with traditional aerobic and/or dynamic resistance

training (1-5). Interesting, it is worthy to note that total power of HRV increased following IHG

exercise in both men and women, which is different to others modalities of exercise. As a result,

IHG is an intervention that can acutely improve cardiac autonomic regulation, which adds weight

to supporting IHG as a promising non-pharmacological therapy for the management of

hypertension (6).

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

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Despite the mounting evidence regarding the beneficial effects of isometric exercise

training on BP management, a recent review of the literature reinforced that the underlying

mechanisms responsible for these adaptations remain largely unknown, though, preliminary data

suggest that changes in cardiac autonomic modulation, sympathetic vasomotor tone, endothelial

dilator function, and oxidative stress may be involved (30). With respect to changes in cardiac

autonomic modulation, a recent study in pre-hypertensive men reported the first evidence of

increased cBRS following acute leg isometric exercise (12). The results of our study extend this

neural response to a single bout of IHG, a much smaller contracting muscle mass, and to a

population of young healthy men and women. Taken together, these findings support the concept

that modulations in the sensitivity of the arterial baroreflex may be one of the mechanisms

involved in the reported reductions in resting BP following IHG training. In contrast, with prior

works (10-12), increases in cBRS occurred independent of acute reductions in arterial BP during

recovery. This could be explained, in part, due the fact that the subjects in our sample were

normotensive and had lower resting BP values. Indeed, previous studies showing acute

reductions in BP following isometric exercise were performed in older adults (10, 11) or pre-

hypertensive subjects (12).

A novel observation of the present investigation is that the time-course and magnitude

of increases in cBRS following acute IHG exercise in healthy normotensive subjects were sex

dependent. Specifically, during the recovery period, cBRS rapidly returned to baseline in men

but remained elevated in women. This sex-related difference in cBRS responses to IHG is not

fully understood. It has been reported that men present higher resting cBRS than women (18-20),

a finding reinforced with the present results. Given this, we can speculate that women may

possess a higher range for increases in cBRS following IHG exercise due to their lower baseline

values compared with men. The present results also suggest that in response to acute IHG, a

stimulus which raises BP, young women may buffer these pressor responses primarily through

changes in cardiac chronotropy (31). This is supported by the persistent reduction in HR

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

Page 13: Sex Differences in Cardiac Baroreflex Sensitivity ... · and women (16, 17). In particular, women present commonly with reduced cardiac baroreflex sensitivity (cBRS), a measure of

throughout recovery in women but not men. In contrast, men may buffer increases in BP

primarily through changes in peripheral vasoconstrictor outflow (31). Importantly, the increased

cBRS gain in women is unlikely to be mediated by female sex hormones (i.e., estrogen and

progesterone) as cyclical fluctuations across the menstrual cycle do not appear to influence cBRS

gain (32) or autonomic modulation (33, 34). Future studies are needed to confirm the role of

female sex hormones on cBRS gain following IHG exercise. Furthermore, it is an interesting

observation that the LF/HF ratio is below baseline at 10 and 30-min post IHG in females

compared with a sustained elevation post IHG in males. These differential autonomic responses

may, in part, be a mechanism for the differences reported in cBRS following IHG exercise and

warrant further investigation. Although men and women presented similar relative effort during

IHG contractions, as confirmed by no significant differences in RPE, we cannot exclude the

possibility that men experienced larger pressor responses during IHG than women (35, 36).

Whether differences in cardiovascular responses during acute IHG impact the sex-differences in

cBRS gain warrants future study.

The present results add to a growing body of literature revealing sex differences in

cardiovascular control during and following a bout of exercise. For example, Wong et al. (37)

demonstrated that during the onset of IHG, women had smaller increases in HR and BP than men

which seemed to be mediated by differential neural activation in several forebrain sites

associated with autonomic regulation. Further, a recent study showed that women exhibit faster

cardiac vagal reactivation following maximum aerobic exercise than age-matched men (38). The

results of these studies demonstrate clearly that cardiovascular responses during and following

exercise can differ between men and women. The present investigation extends this body of

work, demonstrating that acute IHG exercise can increase cBRS, a measure of reflexive vagal

modulations, but that these responses are more pronounced in women.

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

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Clinical implications

The measurement of cBRS is considered to have strong prognostic value for risk

stratification and cardioprotection (39). Several cardiovascular and metabolic disease states are

accompanied by autonomic dysfunction and blunted cBRS (e.g. hypertension, diabetes, heart

failure, coronary artery disease and obesity). Although aerobic exercise training has been shown

to reduce BP and increase cBRS in patients with hypertension (40), the effects of an acute bout

of aerobic exercise on cBRS are less clear. For example, 30 minutes of upright cycling at 65% of

peak oxygen consumption decreased cBRS during recovery in young healthy men (24). In

contrast, our results demonstrate that eight minutes of low intensity IHG can increase

spontaneous cBRS and cardiac parasympathetic activity without altering resting arterial BP.

These transient autonomic responses may be involved in mediating the chronic hypotensive

benefits of IHG training by reducing BP reactivity to stress. Sensitivity of the cardiac baroreflex

has been reported to be inversely related to BP responses to mental stress (41), a predictor of

future BP levels (42). The clinical implications of chronic IHG training warrant further study.

Limitations

The present study has some limitations. First, we studied only young healthy, physically

active, subjects limiting extrapolation of our results to other populations most likely to benefit

from IHG exercise such as older, sedentary and/or diseased patients. Future studies are necessary

to examine the acute effects of IHG on BP control in these populations. Second, cBRS was

calculated based on spontaneous data which assesses a limited range of pressure for the stimulus-

response baroreflex relationship. Perturbational methods, such as the infusion of vasoactive

drugs (i.e. modified Oxford) allow for a more comprehensive examination of the prevailing

range of pressure inputs. However, sequence method has been shown to correlate with the

Oxford technique (43) and studies employing the sequence technique have reported high

reproducibility of spontaneous cBRS at rest and during perturbations (44-46). Third, we

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evaluated a limited range of time following IHG (i.e., 30-min post-exercise). Future studies

should be conducted with more time points to assess the prolonged effect of IHG on BP control,

for example 24-h post-exercise. Fourth, the IHG protocol used was based on prior studies which

showed reductions in arterial BP with training (7-9, 11, 47), but whether it is the most efficacious

for lowering BP, or differs between men and women is unknown.

Conclusion

In summary, we found that IHG exercise acutely improves spontaneous cBRS and

cardiac vagal activity in healthy, young subjects and that these improvements are more

pronounced in women compared with men. These results allow us to suggest that an

enhancement in cBRS may be one of the underlying mechanisms involved in the previously

reported improvements in resting BP control following IHG.

Acknowledgments

The time and effort expended by all the volunteer subjects is greatly appreciated. We thank Luiza

M. Mascarenhas for their excellent support with data collection. This study was in part funded by

CAPES, CNPq and FAPDF. The results of this study are presented clearly, honestly, and without

fabrication, falsification or inappropriate data manipulation and the results of the present study

do not constitute endorsement by ACSM.

Conflict of interest

The authors declare that they have no conflict of interest.

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FIGURE LEGENDS

Figure 1. Cardiac baroreflex sensitivity (cBRS) gain at rest and following one session of

isometric handgrip exercise at 30% (experimental) and 3% MVC (sham) in men (panel A) and

women (panel B). ∗P < 0.05 vs. rest, †P < 0.05 vs. sham protocol.

Figure 2. Percent change from rest (∆) in cardiac baroreflex sensitivity (cBRS) gain following

isometric handgrip exercise at 30% MVC in men (black squares) and women (white squares). ∗P

< 0.05 vs. men.

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Table 1. Baseline characteristics.

Men (n=20) Women (n=20) P value

Age (years) 23 ± 1 24 ± 1 0.46

Weight (kg) 77.9 ± 2.8 58.4 ± 1.5 <0.01

Height (m) 1.78 ± 0.01 1.64 ± 0.01 <0.01

BMI (kg/m2) 24.4 ± 0.8 21.8 ± 0.4 <0.01

MVCabsolute (kg.f)

Right 47.1 ± 1.5 29.6 ± 1.2 <0.01

Left 46.4 ± 1.6 27.9 ± 1.1 <0.01

MVCrelative (kg.f/kg)

Right 0.62 ± 0.01 0.51 ± 0.02 <0.01

Left 0.62 ± 0.02 0.48 ± 0.02 <0.01

Values represents means ± S.E.M. BMI, body mass index; kgf, kilogram-force; MVC, maximum

voluntary contraction (absolute and relative to the body weight). P values are derived from

independent sample t test.

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Table 2. Hemodynamics variables at rest and following 10-, 20- and 30-minutes of isometric handgrip exercise at 30% (experimental)

and 3% (sham) maximum voluntary contraction in men and women.

Men Women P value

Rest 10-min 20-min 30-min Rest 10-min 20-min 30-min Sex Time Conditi

on

Interacti

on

Hemodynamics

HR

(beats.min-1

)

Experimen

tal 66 ± 2 64 ± 2*† 66 ± 2 67 ± 2 75 ± 2‡ 70 ± 2*†‡ 73 ± 2*‡ 73 ± 2*‡ 0.01

<0.00

1 0.12 0.001

Sham 67 ± 1 67 ± 1 67 ± 2 67 ± 1 75 ± 2‡ 74 ± 2‡ 75 ± 2‡ 75 ± 2‡

Systolic BP

(mm Hg)

Experimen

tal 113 ± 2 119 ± 2*† 115 ± 2*† 115 ± 2*† 100 ± 1‡ 103 ± 2*†‡ 101 ± 2†‡ 101 ± 2†‡

<0.00

1

<0.00

1 <0.001 0.04

Sham 112 ± 2 113 ± 2 112 ± 2 113 ± 2 99 ± 2‡ 100 ± 1‡ 98 ± 2‡ 99 ± 1‡

Diastolic BP

(mm Hg)

Experimen

tal 61 ± 1 63 ± 1 62 ± 1 62 ± 1 57 ± 1 59 ± 1 59 ± 1 59 ± 1 0.01 0.01 0.17 0.36

Sham 62 ± 1 62 ± 1 62 ± 1 62 ± 1 56 ± 1 57 ± 1 57 ± 1 59 ± 1

Mean BP

(mm Hg)

Experimen

tal 78 ± 1 81 ± 1 79 ± 1 80 ± 1 71 ± 1 73 ± 1 73 ± 1 73 ± 1

<0.00

1 0.001 0.01 0.22

Sham 79 ± 1 79 ± 1 79 ± 1 79 ± 1 70 ± 1 71 ± 1 70 ± 1 72 ± 1

HR variability

RMSSD (ms)

Experimen

tal 54.7 ± 4.7 62.3 ± 6.5 59.3 ± 5.8 59.5 ± 7.2 40.5 ± 3.1 52.5 ± 4.7 46.5 ± 3.6 46.0 ± 3.3 0.07 0.001 0.06 0.92

Sham 52.0 ± 5.2 51.5 ± 4.5 53.0 ± 5.4 54.8 ± 6.5 42.0 ± 3.2 43.6 ± 3.0 44.2 ± 2.9 42.7 ± 2.9

LF (ms2)

Experimen

tal

1424.7 ±

372.1

2132.2 ±

520.1

2700.8 ±

761.5

2839.4 ±

894.5

996.4 ±

119.0

1325.3 ±

178.1

1390.2 ±

184.9

1323.3 ±

228.4 0.11 <0.01 0.06 0.31

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Sham 1438.1 ±

387.5

1485.5 ±

217.7

1768.8 ±

261.9

2291.0 ±

637.6

929.2 ±

105.9

1075.3 ±

132.4

1290.3 ±

194.8

1285.7 ±

154.2

HF (ms2)

Experimen

tal

1389.3 ±

381.4

1748.6 ±

422.1

1459.0 ±

295.1

1635.5 ±

409.9

860.6 ±

177.6

1391.5 ±

297.2

1087.6 ±

209.6

1037.6 ±

166.0 0.22 0.03 0.15 0.78

Sham 1288.3 ±

423.6

1153.0 ±

315.2

1354.9 ±

281.4

1650.1 ±

452.1

825.1 ±

105.4

874.5 ±

103.3

952.1 ±

132.6

917.5 ±

139.2

Total power

(ms2)

Experimen

tal

3674.1 ±

841.7

4992.9 ±

1071.7

5645.1 ±

1244.4

6262.9 ±

1529.0

2488.2 ±

301.8

3670.8 ±

492.4

3371.0 ±

417.7

3245.4 ±

457.0 0,12 <0.01 0,03 0,08

Sham 3644.7 ±

938.6

3604.7 ±

599.6

4258.6 ±

617.5

5338.0 ±

1237.1

2329.9 ±

233.4

2562.3 ±

236.1

3214.9 ±

379.8

3081.1 ±

324.5

LF/HF

Experimen

tal 1.31 ± 0.18 1.47 ± 0.18 1.94 ± 0.25 2.25 ± 0.36 1.65 ± 0.22 1.31 ± 0.12 1.71 ± 0.20 1.48 ± 0.17 0.46 <0.01 0.30 0.07

Sham 1.69 ± 0.25 2.10 ± 0.40 1.75 ± 0.28 2.07 ± 0.35 1.57 ± 0.29 1.60 ± 0.29 1.70 ± 0.17 1.83 ± 0.24

Values represents means ± S.E.M. HR, heart rate; BP, blood pressure; RMSSD, square root of the mean of the sum of successive

differences in R-R interval of HR variability; LF, low-frequency; HF, high-frequency; LF/HF, ratio between low- and high-

frequency components of HR variability. P values are derived from ANOVA examining main effects of sex, time, condition and

interaction (sex × time × condition). ∗P < 0.05 vs. rest, †P < 0.05 vs. sham protocol, ‡P < 0.05 vs. men.

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