Hemodynamic Responses and the Sustainability of Force during Submaximal Isometric Handgrip Exercise: Are There Sex Differences?

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_____________________________________________________________________________________________________

*Corresponding author: E-mail: [email protected];

(Past name: British Journal of Medicine and Medical Research, Past ISSN: 2231-0614, NLM ID: 101570965)

Hemodynamic Responses and the Sustainability of

Force during Submaximal Isometric Handgrip

Exercise: Are There Sex Differences?

Konstantina Dipla

1*

1

Exercise Physiology and Biochemistry Laboratory, TEFAA at Serres, Aristotle University of Thessaloniki, Agios Ioannis, Serres 62110, Greece.

Author’s contribution

The sole author designed, analyzed and interpreted and prepared the manuscript.

Article Information

DOI: 10.9734/JAMMR/2017/35357 Editor(s): (1)Teodoro Cordova Fraga, University in Guanajuato, Mexico. Reviewers: (1) Naro Ohashi, Hamamatsu University School of Medicine, Japan. (2)Vagner Raso, University of Sao Paulo, Brazil. (3)Ayfer Pazarbasi, Çukurova University, Turkey. Complete Peer review History:http://www.sciencedomain.org/review-history/20702

Received 9th July 2017 Accepted 24th August 2017 Published 28th August 2017

ABSTRACT

Background: Sex related differences in the control of blood pressure at resting conditions have been previously reported. Studies in rodents have also shown that during exercise, female animals have an enhanced capacity to inhibit sympathetic vasoconstriction than male animals.

Aims: To examine whether sex differences exist in (i) systolic/diastolic blood pressure (SBP/DBP) and systemic vascular resistance (SVR) responses during handgrip exercise, (ii) the ability to sustain a predetermined target force during isometric handgrip, in young, healthy, lean adults. Study Design / Methodology: Fourty-six adults (19 men and 27 women), aged 20-27 years, underwent a protocol that included a seated rest (baseline), a 3-min handgrip at 30% of maximal voluntary contraction (MVC), and recovery. Continuous, beat-to-beat SBP/DBP and heart rate were recorded (Finapres). Handgrip force was monitored (Biopac).

Results: Men had higher MVC than women (P < 0.001), however, both sexes exhibited similar handgrip steadiness. Men rated the exercise session as fatiguing as their female counterparts. During baseline, no differences were found between groups in SBP, DBP, and heart rate; however, during exercise and recovery, men exhibited a higher DBP response than females (P < 0.05). SVR

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Dipla; JAMMR, 23(7): 1-11, 2017; Article no.JAMMR.35357

remained relatively stable during handgrip in men, whereas, a decline in SVR during exercise and recovery was observed in women (P < 0.05).

Conclusion: Differential hemodynamic responses during isometric exercise and recovery were revealed between young, healthy, and lean men and women. However, the steadiness and ability to sustain force during isometric exercise were not significantly different between men and women.

Keywords: Gender differences; isometric exercise; blood pressure; hemodynamics; total peripheral resistance; females; force; stability.

1. INTRODUCTION

Sex related differences in the control of blood pressure at resting conditions have been previously reported [1-3]. For most of human life (i.e. up to the fifth decade of life), women have lower resting blood pressure and experience orthostatic hypotension more often than men of similar age [2,4]. In addition, young women show a lower incidence of hypertension than young men [3,5]. Previous studies have also reported that at resting conditions young females exhibit a blunted forearm vasoconstrictor response to adrenergic stimulation, induced by norepinephrine (NE) injection [6,7]. Moreover, estrogen has been shown to increase nitric oxide (NO) synthase expression and NO bioavailability, inducing vasodilatory effects at resting conditions [8-11]. Since women have a greater relative abundance of estrogen compared to men, it seems plausible to suggest that females may have an enhanced potential to inhibit vasoconstriction not only at rest, but also during exercise. In accordance with this view, recent studies in rodents have shown that during exercise, female animals have an enhanced capacity to inhibit sympathetic vasoconstriction (i.e. they exhibit a greater functional sympatholysis) [12].

Exercise training has been widely recommended in the prevention of high blood pressure (BP). Although aerobic exercise has been the traditionally used mode of exercise for hypertension, recent studies suggested that isometric resistance training can also be effectively used to lower resting BP [13-16]. A limited number of studies have investigated whether there are sex-related differences in the hemodynamic control of blood pressure during resistance exercise, and even fewer during isometric handgrip exercise [17]. Furthermore, during isometric handgrip exercise, the contracting muscles exert a sustained mechanical compression on the blood vessels. This causes a transient restriction of inflow in the exercising muscles, and possibly contributes to

the marked increases in blood pressure (BP) observed during this mode of exercise. As men exhibit a greater handgrip force in absolute terms than women, and possibly a greater mechanical compression of their vessels during sustained contractions, it was hypothesized that men will exert a greater restriction of blood flow during exercise. In turn, this inflow restriction could induce not only greater hemodynamic responses, but could also a limit the ability to maintain steady force, resulting in earlier signs of fatigue during a submaximal handgrip test compared to women. Therefore, the purpose of this study was to examine if sex differences exist in (i) the systolic/diastolic BP and the systemic vascular resistance (SVR) responses during handgrip exercise, (ii) the ability to sustain a predetermined target force during isometric handgrip in young, healthy, and lean adults. It has been hypothesized that women will possibly exert a differential hemodynamic control during exercise, exhibiting a blunted change in SVR than men. It has also been hypothesized that women will be able to sustain a greater percentage of their target force, with greater stability than men. For these purposes, beat-by-beat hemodynamic responses at rest, during handgrip exercise, and recovery were assessed in young men and women. Force was continuously recorded during a sustained 3-min handgrip exercise. Examination of sex related differences in cardiovascular responses, stability, and perceived exertion during isometric handgrip exercise could allow for more optimized sex-based isometric exercise prescription, and thereby maximize the effectiveness of the isometric exercise training.

2. MATERIALS AND METHODS

2.1 Participants

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index <25 kg/m2, and were recreationally active. The study was conducted in accordance with the Declaration of Helsinki and approved by department’s review board committee. Before the study, all participants were informed about the aims and study procedures and gave their written informed consent. Participants were non-smokers, because acute and chronic smoking can alter exercise hemodynamics [18]. Participants were also instructed to avoid intense physical activity the previous day before testing. Participants were instructed not to consume coffee, tea and alcohol for 12 hours before testing. Women were tested in different phases of their menstrual cycle (so that an equal number of women were in the follicular and in the luteal phase), but not during menstruation.

2.2 Testing Procedures and

Instrumentation

Participants arrived in the laboratory in the morning hours. After obtaining a personal and family history, anthropometrical characteristics were assessed. The participant was then connected to the experimental apparatus for assessment of hemodynamics. More specifically, the participant was connected to the finger photoplethysmography apparatus (Finometer, Finapres Medical Systems, Amsterdam, The Netherlands) for continuous, beat-to-beat assessment of systolic and diastolic arterial pressure (SAP/DAP) and heart rate. The finger cuff of the Finapres apparatus was placed on the middle finger and the inflatable cuff was placed at the heart level on the non-dominant arm.

Following calibration (for approximately 12 min) and baseline (for 5 min) measurements with the participant in the seated position, the handgrip exercise protocol started. Initially, the participant’s maximal handgrip strength was assessed using a Biopac dynamometer (MP150, CA, USA). Each participant performed three maximal voluntary contractions (MVC) with the dominant hand, with the elbow flexed at 90°, and a 60-s rest between trials. The highest reading of the three trials was considered as the MVC. After that, a 3-min isometric handgrip exercise was performed, during which the participant was required to maintain his/her 30% MVC. Visual feedback on a monitor was provided to the participant and specific instructions were given, in order to maintain force as steady as possible. The participant was constantly instructed to avoid the Valsalva maneuver and keep non-participating muscles relaxed. A 5-min recovery followed. The participant’s rate of perceived

exertion was evaluated using the Borg scale (6-20).

Finapres and biopac data were stored on computers for offline analysis. Stroke volume was calculated non-invasively using the Modelflow method, an arterial pressure wave analysis which has been shown to be a reliable alternative to invasive thermodilution techniques [19,20]. Systemic vascular resistance was calculated as mean BP / cardiac output using the BeatScope software, version 1.a. The magnitude of change from baseline (delta) in systolic and diastolic blood pressure, during handgrip exercise, and recovery was also calculated (i.e. delta SAP handgrip: SAPexercise – SAPbaseline;

delta DAP: DAPexercise – DAPbaseline; delta SAP

recovery: SAPrecovery – SAPbaseline; delta DAP:

DAPrecovery – DAPbaseline. SVR data were

normalized for body surface area (BSA) and reported as systemic vascular resistance index (SVRI). Average force maintained and the standard deviation of force (i.e. stability) during handgrip was calculated by AcqKnowledge 3.9.1 software.

2.3 Statistical Analysis

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hemodynamic variables and force (MVC, force maintained). A P < 0.05 was considered as statistically significant.

3. RESULTS AND DISCUSSION

3.1 Participants’ Characteristics

Nineteen normotensive young men, aged 21.8 ± 1.5 years and twenty seven young women 21.14 ± 1.99 years participated in the study. Men had higher body weight and body mass index (BMI) than females (body weight: 77.2±9.8 vs. 59.6±8.3 kg; BMI: 24.0±2.1 vs. 22.0 ± 2.6 kg/m2; P < 0.01).

3.2 Isometric Handgrip Strength and Stability

Men had higher MVC than women (54.9 ± 9.7 vs. 34.6 ± 7.5 kg, respectively; P < 0.001). The statistically significant difference in MVC between men and women persisted when MVC data were normalized for BMI (i.e. handgrip kg/body weight kg/m2; 2.3 ± 0.5 vs. 1.6 ± 0.3, P < 0.001). During the 3-min exercise, men maintained a higher absolute force than women (13.8 ± 3.1 vs. 8.2 ±2.6 kg, respectively; P < 0.001). However, men and women did not differ in the percentage of their MVC maintained during the 3-min handgrip (25.2 ± 4.6 and 23.5 ± 4.5%, in men and women, respectively; P = 0.21; Fig. 1A). Men and women exhibited a similar steadiness in their grip, in absolute terms (2.4 ±1.5 and 2.2 ± 2.3 kg, respectively; P = 0.9; Fig. 1B) and in relative

terms (i.e. normalized for MVC: 0.04 ± 0.02 and 0.06 ± 0.06, respectively; P = 0.13). Men rated the exercise session as fatiguing as their female counterparts (15.9 ± 2.0 and 15.3 ± 0.8, respectively; P = 0.42).

3.3 Hemodynamic Responses

3.3.1 Blood pressure and heart rate responses

Average data for SAP, DAP, and heart rate per testing period in the two groups, are presented in Fig. 2. During baseline, there were no significant differences between groups in SAP, DAP, and heart rate (SAP: 127.2 ±10.7 vs. 122.9 ± 9.3 mmHg; DAP: 79.0 ± 7.1 vs. 74.8 ± 5.8 mmHg; heart rate: 67.8 ±9.2 vs. 74.9 ± 10.2 bpm, respectively).

During isometric exercise, SAP and DAP significantly (P < 0.001) increased within each group (SAP: 161.5 ± 16.4 and 154.2 ± 12.3 mmHg, DAP: 102.3 ± 12.5 and 95.3 ± 6.7 mmHg, in men and women, respectively). Although during exercise there were no statistically significant differences between groups in SAP (P = 0.29), men exhibited significantly higher DAP values than women (P = 0.03). Heart rate significantly increased during exercise compared to baseline in both groups (96.9 ±17.9 vs. 103.4 ±14.5 bpm, males and females, respectively, P <0.001), without statistically significant differences between groups (P = 0.4).

Fig. 1. (A) Percentage of maximal voluntary contraction maintained during the 3-min handgrip and (B) Stability of force during the 3-min handgrip exercise (standard deviation of force

maintained) 10

20 30

B Men Women

Perc

ent

a

ge

of Force

Mai

ntai

ned

(%)

Men Women

A

0 2 4

S

tandar

d

dev

ia

tio

n of

force ma

intai

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Fig. 2. Absolute values in (A) systolic blood pressure, (B) diastolic blood pressure, and (C) heart rate responses during rest, handgrip exercise, and recovery in men and women

*P < 0.05 vs. baseline, † P < 0.05 vs. men in the respective period

During recovery, SAP declined compared to the HG values (141.2 ± 11.7 and 131.3 ± 10.43 mmHg, in men and women respectively), but remained higher than baseline in both groups. SAP during this period has slightly higher in men than women; however, this difference was not statistically significant (P = 0.07). DAP also declined during recovery, in both groups, however, it remained higher than baseline in men. In contrast, DAP returned to baseline in women, with men exhibiting greater values than women (83.8±7.7 vs. 76.5±5.4 mmHg, respectively; P < 0.024) during this period. Heart rate was not different between men and women during recovery (69.1 ± 11.00 and 75.0 ± 9.7 beats per min).

Next, the magnitude of increase in BP from baseline (delta-SAP and delta-DAP) during exercise and recovery, was calculated. A significant main effect of gender was been revealed in the magnitude of responses during exercise in BP (that is, main effect of gender in

delta-SAP p=0.039, partial η2 =0.09, medium effect size; main effect of gender in delta-DAP p=0.017, partial η2 =0.12, medium-large effect size) responses (Fig. 3).

3.3.2 Systemic vascular resistance responses

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0.013). More specifically, in males, SVRI remained stable during the protocol (

0.132, 0.532 ± 0.186, and 0.535 ±

during baseline, exercise, and recovery, respectively; P = 0.98); however, in females SVRI decreased during exercise compared with baseline levels (P <0.001) and remained lower (P <0.01) than exercise during recovery (

Fig. 3. Magnitude of change from baseline (delta) in (A) systolic and (B) diastolic blood pressure, during handgrip exercise, and recovery in men and women

*P < 0.05 significant main effect of gender (i.e.

Fig. 4. Correlation of the magnitude of change from baseline (delta) in (A) systolic and (B) diastolic blood pressure during handgrip exercise with maximal voluntary contraction in men

and women (R = 0.13 and R = 0.16,

0 5 10 15 20 25 30 35 40 45 50 55 60 65

D

elta Sy

s

tol

ic B

lood P

res

sure

(

m

mHg)

*

H a nd grip R ecovery

A

Dipla; JAMMR, 23(7): 1-11, 2017; Article no.

0.013). More specifically, in males, SVRI remained stable during the protocol (0.545 ± ± 0.134 MU/m2, during baseline, exercise, and recovery, respectively; P = 0.98); however, in females SVRI decreased during exercise compared with baseline levels (P <0.001) and remained lower (P <0.01) than exercise during recovery (0.719 ±

0.229, vs. 0.628 ± 0.193, 0.651 MU/kg/m2, during baseline, exer

recovery, respectively). Furthermore, the magnitude of change from baseline in SVRI during exercise was significantly greater in men than women (0.014 ± 0.10 vs. 0.091 ± 0.10 MU/kg/m2; main effect of gender in delta p=0.05, partial η2 = 0.09, medium effect size).

*P < 0.05 significant main effect of gender (i.e. men vs. women)

A

and women (R = 0.13 and R = 0.16, respectively; P > 0.05) R ecovery

0 5 10 15 20 25 30 35

M ales F em ales

Delt

a Di

astolic

B

loo

d

Pre

s

u

re (mmH

g)

H a nd grip R ecovery

*

B

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0.229, vs. 0.628 ± 0.193, 0.651 ± 0.186 during baseline, exercise, and recovery, respectively). Furthermore, the magnitude of change from baseline in SVRI during exercise was significantly greater in men than women (0.014 ± 0.10 vs. 0.091 ± 0.10 ; main effect of gender in delta-SVRI: 9, medium effect size).

B

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No significant correlation was observed between the magnitude of increase in BP during exercise (delta-SAP and delta-DAP) with MVC or with the force maintained during handgrip (delta-SAP with MVC: R = 0.13, P = 0.39 and delta-DAP with MVC: R = 0.16, P = 0.29; delta-SAP with force

maintained: R = 0.09, P = 0.53 and R = 0.15, P = 0.30; Fig. 4). In addition, the magnitude of

change in SVRI during exercise, was not significantly correlated with MVC (R = 0.052, P = 0.74) and with the force maintained during handgrip (R = 0.06, P = 0.7).

3.4 Discussion

The results of this study showed that women exhibited lower DAP response during isometric exercise at 30% MVC and a faster recovery to baseline levels compared with men. In addition, a differential response in SVR between sexes was observed, with women exhibiting a reduction in SVR during exercise and recovery, whereas, SVR remained unaltered in men throughout the protocol. Although during handgrip exercise men exerted a greater force in their forearm muscles in absolute terms than women, no differences in the steadiness of handgrip and in the rate of perceived exertion were found between groups.

In this study, all participants were normotensive and no baseline differences in BP and heart rate were observed between groups. The slightly higher, non-statistically significant differences in SVR observed in women, are in accordance with previous studies [2]. Only lean individuals were recruited for this study, as obesity can alter the hemodynamic/neural responses to exercise, even in young individuals [21-23]. Testing in women was performed in different phases in their menstrual cycle with an equal number of women being in follicular and in luteal phase, so that the results of the study apply in women in both phases of the menstrual cycle. Women were not tested during the menstrual phase, so that hemodynamic responses are not influenced by differences in fluid loss or dehydration among the participants.

The isometric handgrip exercise used in this study, is a physiological excitatory stimulus of the sympathetic nervous system. During handgrip, the control of circulation depends on the interaction of neural stimuli i.e. signals from higher brain centers (originating in the brain’s

motor cortex, termed as central command) and peripheral afferents (baroreceptors,

mechanoreceptors, and metaboreceptors), as

well as, local vasodilatory factors released during exercise (such as NO and ATP) [24-32]. The interplay of these stimuli regulates cardiac output and peripheral resistance and results in an effective elevation of blood pressure, in an attempt to supply the working muscles with the required oxygen [33]. The selection of the exercise intensity in this study, was based on previous results, showing that exercise at 30% MVC activates both the mechanoreflex and the metaboreflex components of the exercise pressor reflex and allows force to be maintained for about 3 min [18,34-36]. This exercise intensity (30% MVC) has also been used in studies using isometric handgrip as the mode of chronic training [37]. All participants in the present study were able to complete the 3-min protocol, with no differences in the rating of perceived exertion observed between groups.

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showed a greater reduction in resting DAP than men [41].

The differential response in SVR during isometric exercise between men and women possibly suggests a greater functional sympatholysis in women. Functional sympatholysis, defined as the diminished vasoconstriction to increased sympathetic activity that occurs in the working muscles during exercise, has been previously attributed to at least two possible mechanisms [31,42]. The first proposed mechanism is that NO synthase is activated in the contracting muscle and releases NO, which in turn acts on vascular smooth muscle or endothelial cells to oppose the activation of α1- and α2-adrenergic receptors by NE, attenuating vasoconstriction; while the second mechanism involves ATP, released from both muscle and deoxygenated hemoglobin that activates the purinergic receptors, acting again on vascular smooth muscle or endothelial cells and attenuates vasoconstriction [32,43-45]. In a recent study in rats, an enhanced functional sympatholysis was observed in female compared to male rats mediated by an NO dependent mechanism. However, the exact mechanism in humans requires further research.

In line with the present findings showing that a differential response of blood vessels (i.e. a reduction in SVR) during isometric exercise in females and not in males, a previous study by Collier showed that following chronic resistance training, women did not experience the increase in arterial stiffness (assessed using pulse wave velocity) that was observed in men [41]. Thus, our findings point to different integrated physiological mechanisms to maintain a normal BP during exercise between healthy, young, lean men and women. A limitation of this study is that individual blood estrogens and progesterone levels were not measured; thus, it can only be speculated that estrogen-mediated effects on the vasculature play a role in the present findings. Future studies should be conducted to examine the association of estrogen levels to the SVR responses during exercise. Another limitation of this study is that SVR responses were calculated from the beat-by-beat Finapres recordings and not directly measured with a catheter. The Finapres photophlethysmographic technique however, has the merit of being non-invasive, and has been proven to be valid both at rest and during exercise [46,47]. Finally, men exhibited greater force during handgrip than women. Thus, the greater force maintained could be partially

contributed to the greater increase in exercise DAP. However, the magnitude of increase in BP and in SVR in this study, were not significantly correlated with MVC nor with the force maintained during handgrip. In addition, differences in force exerted between men than women, were evident even when differences in body size are taken into account (i.e. when force was normalized for body size). Therefore, this greater force is an intrinsic characteristic of men. Choosing men and women with similar force to investigate gender differences in force stability could have assisted to isolate a gender effect, however, the selection of the participants in the two groups would not have been representative of the two populations.

In contrast to our hypothesis that men will show a greater variability in their force production (due to their greater, in absolute terms, compressive mechanical forces, limiting muscle hyperemia in the exercising forearm) compared to women, no differences in force stability were observed between groups. It has been previously shown in vitro studies and in healthy men that the mechanical stress to erythrocytes and endothelial cells may stimulate ATP release [48]. Whether blood and/or endothelial cells or enhanced local deoxygenation in men increase more intravascular ATP release during exercise, permitting local blood perfusion to the same level as in women, requires further investigation [49]. Furthermore, other mechanisms such as motor cortex activation, cerebral oxygenation, and central command that are involved in the ability to sustain handgrip force also require further study. In addition, since in this study participants were young, healthy, and lean adults, future studies should examine whether these findings apply to individuals with hypertension and other chronic disease.

4. CONCLUSION

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CONSENT

A written informed consent was obtained from each participant.

ETHICAL APPROVAL

All experiments have been examined and approved by the appropriate ethics committee and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

COMPETING INTERESTS

Author has declared that no competing interests exist.

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