Rate of rise in diastolic blood pressure influences vascular sympathetic response to mental stress (2024)

• Research indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress.

• In this study, we examined the early blood pressure responses (including the peak, time of peak and rate of rise in blood pressure) to mental stress in positive and negative responders.

• Negative MSNA responders to mental stress exhibit a more rapid rise in diastolic pressure at the onset of the stressor, suggesting a baroreflex‐mediated suppression of MSNA. In positive responders there is a more sluggish rise in blood pressure during mental stress, which appears to be MSNA‐driven.

• This study suggests that whether MSNA has a role in the pressor response is dependent upon the reactivity of blood pressure early in the task.

Abbreviations

BP

blood pressure

BRS

baroreflex sensitivity

DBP

diastolic blood pressure

ECG

electrocardiogram

MAP

mean arterial pressure

MSNA

muscle sympathetic nerve activity

MVC

maximal voluntary contraction

RMS

root mean square

SBP

systolic blood pressure

Ethical approval

The study was conducted with the approval of the Human Research Ethics Committee, Western Sydney University, and conformed to the Declaration of Helsinki. Written consent was obtained and participants were informed that they could withdraw from the experiment at any time.

Participants

Twenty‐four healthy male participants aged between 18 and 25years, with no history of cardiovascular disease, were recruited for the study. Participants were asked to refrain from rigorous exercise and the consumption of alcohol for a minimum of 24h prior to the experiment and from the consumption of caffeine on the day.

Measurements

All experiments took place in a temperature‐controlled laboratory (22–23°C) under quiet conditions. Participants were studied in a semi‐reclined posture with their legs supported in the extended position. Continuous MSNA recordings were made from muscle fascicles of the common peroneal nerve supplying the ankle and toe extensor and foot evertor muscles via tungsten microelectrodes (FHC, Bowdoin, ME, USA) inserted percutaneously at the level of the fibular head. During intraneural stimulation (0.2ms, 1Hz, 1mA), muscle twitches indicated that the microelectrode was approaching a muscle fascicle. Twitches at 0.02mA or below signified entry into a muscle fascicle, along with stretch‐evoked muscle spindle afferent activity and a lack of cutaneous sensations. Sympathetic bursts possessed a clear cardiac rhythmicity, increased with inspiratory apnoea, demonstrated baroreflex modulation (increased with a fall in pressure and decreased with a rise in pressure), and could not be evoked by a brisk sniff or sudden loud shout, thus differentiating them from skin sympathetic activity (Mano etal. 2006; El Sayed etal. 2012). Multi‐unit neural activity was amplified (gain 20,000, bandpass 0.3–5.0kHz) using an isolated amplifier and headstage (NeuroAmpEX, ADInstruments, Sydney, Australia) and stored on a computer (10kHz sampling) using a computer‐based data acquisition system (PowerLab 16SP hardware and LabChart 7 software; ADInstruments). A root‐mean‐square (RMS) processed version of the signal was computed with a moving average of 200ms. Blood pressure was recorded non‐invasively, via finger pulse plethysmography (Finometer; Finapres Medical System, Amsterdam, the Netherlands) sampled at 400Hz. Electrocardiographic (ECG) activity was recorded with Ag–AgCl surface electrodes on the chest sampled at 2kHz, and respiration was recorded via a strain‐gauge transducer (Pneumotrace, UFI, Morro Bay, CA, USA) wrapped around the chest, sampled at 0.4kHz.

Experimental procedures

Once a stable MSNA recording site was achieved with spontaneous neural activity, the participants were asked to relax, while controlled baseline cardiovascular measurements were recorded for 10min. Following the initial 10min baseline period, participants completed two mental and three physical stressor tasks. The mental tasks performed were mental arithmetic and the Stroop colour‐word conflict test, and the physical tasks performed were a cold pressor test, static handgrip exercise and post‐exercise ischaemia. Each task lasted for 2min and was performed in a randomised order with the exception of post‐exercise ischaemia, which immediately followed the handgrip task. Stressor tasks were separated by a minimum of 5min rest (with additional time if required) to ensure that all variables were stable before commencing the next task.

Mental arithmetic task: Participants were given a three‐digit starting number and asked to consecutively subtract seven, verbally stating their answers for a period of 2min. If the participants gave an incorrect answer, they were notified and reminded of the last correct number; if their answer was correct they continued without feedback. The number of correct numbers was recorded. On completion of the task, participants were asked to rate their anxiety levels experience during the task on a scale of 0 (no anxiety) to 10 (most anxious I have felt).

Stroop colour‐word conflict test: Using an iPad with a Stroop colour‐word application, participants were required to respond via touch‐screen with the correct colour of the word displayed on the screen (as opposed to the colour the word spells out). The number of correct answers was recorded. On completion of the task, participants were asked to rate their anxiety levels on a scale of 0 to 10.

Cold pressor test: Participants were required to immerse their dominant hand in ice water for a period of 2min. During the task the participants were asked to record their pain level using a visual analogue scale; 0 describes ‘no pain’ while 10 describes ‘the worst pain imaginable’.

Static handgrip exercise: A handgrip dynamometer was calibrated according to each participant's maximal voluntary contraction (MVC). Participants were instructed to grip the handgrip dynamometer at 35% MVC for 2min. The %MVC was displayed on the computer screen to provide feedback to the participants.

Post‐exercise ischaemia: Five seconds prior to the cessation of handgrip exercise, a cuff was inflated around the active arm to 200mmHg in order to occlude blood flow to the contracting muscles. The cuff remained inflated for 2min while the participant relaxed their arm. The cardiovascular reactivity to post‐exercise ischaemia was treated as a separate task to handgrip exercise.

Data analysis

Sympathetic baroreflex sensitivity

Sympathetic baroreflex sensitivity (BRS) was assessed in all participants. The 10‐min rest period at the beginning of the experimental protocol was used for quantifying sympathetic BRS via spontaneous methods (Kienbaum etal. 2001; Hissen etal. 2015). For each participant, the diastolic pressure values for each cardiac cycle were assigned to 3mmHg bins to reduce the influence of respiratory‐related oscillations (Ebert & Cowley, 1992; Tzeng etal. 2009). For each bin the corresponding MSNA burst incidence was determined (number of bursts per 100 cardiac cycles). MSNA burst incidence was plotted against the mean diastolic blood pressure for each bin in order to quantify sympathetic BRS via linear regression. A weighting was applied to account for the number of cardiac cycles associated with each bin (Kienbaum etal. 2001). The acceptance level for baroreflex slopes was set at r>0.5 (Hart etal. 2011; Taylor etal. 2015). Independent ttests were performed to test for differences in sympathetic BRS between positive and negative responders. All statistical analyses were performed using Prism v6.00 for Mac OS X (GraphPad software, San Diego, CA, USA). A probability level of P<0.05 was regarded as significant. All values are expressed as means and standard error of the mean (SEM).

Table 1

Resting sympathetic and cardiovascular variables prior to stressor tasks

Mental arithmetic

When all subjects were pooled mental arithmetic and the Stroop test were both associated with significant increases in systolic blood pressure, diastolic blood pressure, MAP and heart rate (P<0.05, Table 2). There was a significant main effect of time on total MSNA for the mental arithmetic task. Pairwise comparisons revealed that total MSNA was significantly greater than baseline during the final 15s of the task and during the recovery. There was an increase in MSNA burst amplitude, but this did not reach statistical significance (P=0.08; Table 2). There was no significant main effect of time on MSNA burst frequency (P=0.56).

Across the group, 13 individuals demonstrated a mean increase in MSNA burst frequency (positive responders), and eight individuals demonstrated a mean decrease in response to mental arithmetic (negative responders). When grouped according to changes in total MSNA during mental arithmetic, 10 individuals were classified as positive responders and 11 as negative responders. There was no significant difference in the mean change in systolic BP, diastolic BP or MAP between the two groups, regardless of whether they were grouped via MSNA burst frequency or total MSNA (P>0.05; Table 3). Figure1 illustrates the early responses to mental arithmetic in a positive and negative responder (classified via MSNA burst frequency). Whilst the magnitude of the peak changes in BP did not differ between positive and negative responders (P>0.05), the rate of rise in diastolic BP during the first minute of mental arithmetic was significantly greater in negative responders, when classified via response in both MSNA burst frequency (P=0.03) and total MSNA (P=0.04; Table 3; Fig.2). There were significantly earlier peaks in DBP in negative responders (classified by total MSNA response) and MAP (classified by MSNA burst frequency response, P>0.05; Table 3). The time courses of blood pressure and MSNA responses in positive and negative responders to the mental arithmetic task are illustrated in Fig.3, in which the lag in the diastolic BP response can be seen in the positive responders. When the analyses between positive and negative responders were repeated using the extremes, i.e. increases/decreases in MSNA burst frequency of ≥ 3 burstsmin^–1 (Carter & Ray, 2009), the rate of rise in diastolic BP was still greater in negative responders (1.5±0.5mmHgs⁻¹; n=7) versus positive responders (0.4±0.2mmHgs⁻¹; n=6) but this did not reach statistical significance (P=0.09). The magnitude of the peak in diastolic BP was significantly greater in negative responders (14±2mmHg) than positive responders (7±2mmHg; P=0.03). The peak in MAP was also significantly higher in negative responders (17±2mmHg) than positive responders (9±3mmHg; P=0.04).

The analyses were repeated using the peaks in BP during the first 30s (Table 4) and the full 2‐min stressor task (Table 5). During the first 30s of the mental arithmetic task, negative responders had significantly greater peaks than positive responders (grouped by MSNA burst frequency) in systolic BP (27±7 vs. 13±3mmHg; P=0.047), diastolic BP (13±1 vs. 6±1mmHg; P=0.0008) and MAP (16±2 vs. 8±2mmHg; P=0.02). Negative responders also experienced a greater rate of rise in systolic BP (4.9±1.3mmHgs^–1) than positive responders (1.1±0.5mmHgs^–1; P=0.005), with a trend for a greater rate of rise in MAP (2.6±0.8 vs. 1.1±0.4; P=0.08). When peaks in BP were determined from the entire 2‐min task, there was a significantly greater rate of rise in systolic BP in negative responders (2.3±1.0mmHgs⁻¹) than positive responders (0.5±0.1mmHgs⁻¹; P=0.03). There was also a trend for a greater rate of rise in diastolic BP in negative responders (1.4±0.7mmHgs⁻¹) than positive responders (0.7±0.3mmHgs⁻¹; P=0.09).

Stroop test

Perceived anxiety levels (rated out of 10) were significantly higher for mental arithmetic (4.6±0.4) than for the Stroop test (2.9±0.6; P=0.006), which was not associated with significant changes in MSNA when the participants were pooled (P>0.05). For the Stroop test 13 individuals demonstrated a mean increase in MSNA burst frequency (positive responders), of which eight also experienced an increase during mental arithmetic. Eight individuals demonstrated a mean decrease in MSNA burst frequency during the Stroop test (negative responders), of which three also experienced a decrease during mental arithmetic. When grouped according to changes in total MSNA there were eight positive responders (six were also positive responders to mental arithmetic) and 13 negative responders (nine were also negative responders to mental arithmetic). There was no significant difference in the mean change in systolic BP, diastolic BP or MAP between positive and negative responders, whether grouped via MSNA burst frequency or total MSNA (P>0.05; Table 3). During the first minute of the Stroop test, the magnitude of the peak change and the rate of the rise in DBP were significantly greater in negative responders (classified by MSNA burst frequency response, P<0.05; Table 3; Fig.2). When classified by response in total MSNA negative responders experienced an earlier peak and a greater rate of rise in MAP (P<0.05). The rate of rise in DBP was also greater in negative responders although this did not reach significance (P=0.06). The time courses of blood pressure and MSNA responses in positive and negative responders to the Stroop test are illustrated in Fig.4. When the analyses between positive and negative responders were repeated using the extremes, the rate of rise in diastolic BP was still greater in negative responders (1.5±0.5mmHgs⁻¹; n=7) versus positive responders (0.5±0.3mmHgs⁻¹; n=9) but this did not reach statistical significance (P=0.08).

During the first 30s of the Stroop test, negative responders (grouped via MSNA burst frequency) experienced greater peaks than positive responders in diastolic BP (16±3 vs. 7±2mmHg; P=0.01) and MAP (18±4 vs. 8±2mmHg; P=0.02; Table 4). When peaks in BP were determined from the entire 2‐min task, negative responders experienced greater peaks in diastolic BP (32±11mmHg) than positive responders (12±3mmHg; P=0.048; Table 5). There were also trends for greater peaks in systolic BP and MAP in negative responders, and there was a trend for a greater rate of rise in diastolic BP in negative responders (1.2±0.4mmHgs⁻¹) compared with positive responders (0.6±0.2mmHgs⁻¹), but these did not reach significance (P=0.09).

Mental stressors, performance/anxiety and sympathetic baroreflex sensitivity

There was no significant relationship between mean changes in MAP and performance scores for the mental arithmetic task (r²=0.04; P=0.36) or the Stroop test (r²=0.001; P=0.87). There was also no significant relationship between mean changes in total MSNA and performance scores for mental arithmetic (r²=0.13; P=0.11) or the Stroop test (r²=0.002; P=0.84). Perceived anxiety during the stressors was not associated with mean changes in MAP or total MSNA for either task (r²=0.03–0.05; P>0.05). There were no significant differences in anxiety levels during mental arithmetic between positive (4.3±0.6) and negative responders (5.0±0.5; P=0.41). Similarly, there were no significant differences in anxiety levels during the Stroop test between positive (2.5±0.3) and negative responders (3.5±1.1; P=0.28). There were no significant differences in sympathetic BRS between positive (–1.4±0.1bursts (100hb)^–1mmHg^–1) and negative responders (–1.8±0.3bursts (100hb)^–1mmHg^–1; P=0.20) to mental arithmetic. There were no significant differences in sympathetic BRS between positive (–1.5±0.2bursts (100hb)^–1mmHg^–1) and negative responders (–1.6±0.2bursts (100hb)^–1mmHg^–1) to the Stroop test.

Physical stressors

The physical stressors elicited large and consistent increases in blood pressure amongst participants. Typical recordings obtained during the cold pressor test are shown in Fig.5. It can be seen that parallel increases occurred in MSNA and blood pressure during the test. There were significant main effects of time on blood pressure, heart rate, total MSNA, MSNA burst frequency and mean MSNA burst amplitude in response to both the cold pressor test and handgrip exercise (P<0.05; Table 2). As expected, during the period of post‐exercise ischaemia, heart rate returned to baseline levels, whilst blood pressure, total MSNA and MSNA burst amplitude remained elevated above baseline (P<0.05). MSNA burst frequency was not significantly different from resting levels (P=0.13). Figure6 illustrates the time course of blood pressure and MSNA responses during the physical stressor tasks. In the cold pressor task, there were gradual and concurrent increases in blood pressure and total MSNA over the 2min. These increases were consistent between individuals as indicated by the small error bars (Fig.6). The average peak pain score during the task was 6.5±0.5 out of 10. Linear regression analysis revealed no significant relationship between pain score and the mean change in MAP (r²=0.03; P=0.46). The linear relationship between pain score and mean change in total MSNA failed to reach significance (r²=0.15; P=0.09). For the static handgrip task, the gradual increases in blood pressure were paralleled by the increases in total MSNA and MSNA burst frequency. Since the cold pressor, handgrip and ischaemia tasks elicited consistent increases in MSNA between participants, no analyses on positive and negative responders were performed for physical stressors.

Inter‐individual differences in MSNA responses to mental stress

Consistent with previous studies (Carter & Ray, 2009; Yang etal. 2013; Dunn & Taylor, 2014), mental stress was associated with significant increases in blood pressure and heart rate. However, in contrast to physical stressors, there was considerable inter‐individual variability in MSNA responses to mental stressors. For the first time, this study characterises the time course of MSNA and blood pressure responses to mental stress in healthy young males, taking into account the direction of the change in MSNA in each individual.

When responses for the 21 males were pooled, mental arithmetic was only associated with a significant change in MSNA during the last 15s of the task and during recovery, and the Stroop test was not associated with significant changes in MSNA at all. This lack of significant response may be due to the similar numbers of positive and negative responders within the group. In some individuals there is an overshoot in MSNA during recovery to above resting levels. Elevated MSNA in the recovery following mental stress has been demonstrated in several studies (Anderson etal. 1987; Callister etal. 1992; Kamiya etal. 2000; Carter etal. 2004, 2005, 2007), and may be explained by a baroreflex‐driven increase in MSNA in response to the fall in pressure following completion of the mental stressor task. The MSNA response is exaggerated because the baroreflex was reset to higher pressures during stress (Durocher etal. 2011; Fonkoue & Carter, 2015).

The baroreflex may also explain the inter‐individual variability in MSNA responses during mental stress. Although sympathetic BRS did not differ between positive and negative responders, the stimulus the baroreflex received in the early stages of the stressor tasks did. It is clear from the current study and previous research that individuals may experience a rise or fall in MSNA. Our findings suggest that the direction of the MSNA response is associated with the rate at which blood pressure rises during stress. Specifically, the rate of rise in diastolic blood pressure is greater in those individuals who demonstrate a reduction in MSNA. The sympathetic baroreflex serves to regulate blood pressure by adjusting MSNA in response to acute changes in diastolic blood pressure. During mental stress the sympathetic baroreflex is reset and baroreflex sensitivity is also lower in the first 2min of the task (Durocher etal. 2011). Under these conditions, the lag in the rise in blood pressure in positive responders would allow MSNA to rise due to less baroreflex inhibition. In contrast, a brisk rise in blood pressure in negative responders caused by non‐MSNA mechanisms may occur concurrently with baroreflex resetting and thus the baroreflex suppresses MSNA. These mechanisms cause blood pressure to remain elevated above baseline in these individuals despite the suppression of MSNA.

Classic studies of the haemodynamic responses to stressors such as handgrip exercise have demonstrated that a pressor response consistently occurs regardless of the mechanism behind it; if one element of the autonomic nervous system is unavailable then it is compensated for by another (Martin etal. 1974). The rise in blood pressure, deemed an appropriate physiological response to handgrip exercise, may be driven by increases in MSNA, elevated cardiac output, reduced baroreflex sensitivity and/or resetting, or a combination of these factors. If the same applies to mental stress then an increase in blood pressure will occur regardless of whether it is driven by MSNA or whether MSNA is suppressed and another mechanism takes over. The current study suggests that the role of MSNA is dependent upon the early response in blood pressure. Negative MSNA responses to mental stress are associated with more rapid increases in diastolic blood pressure, suggesting that the baroreflex suppresses MSNA and an alternative driving factor is responsible for the rise in blood pressure. If the blood pressure response at the onset of mental stress is sluggish then MSNA increases (i.e. a positive response) and contributes to the rise in pressure.

Rate of rise analysis

The aim of our analytical approach is to identify the peak in BP and when it occurs, and to determine from this the rate of the rise during stress. In this study, the influence of the rate of rise in pressure and the differences between positive and negative responders are clearest and most consistent for the mental arithmetic task. Mental arithmetic was associated with greater anxiety levels and greater elevations in blood pressure than the Stroop test, and may explain the ability to detect more distinct differences between groups. The use of extreme stress has ethical implications in human research and thus appropriate limits must be adhered to. It may be speculated that tasks that are deemed to be more stressful provide a greater stimulus and may well evoke larger and potentially more robust responses between individuals. Whilst other tasks, such as making a speech, have also been used in mental stress research (Lipman etal. 2002) and may be considered more stressful, the most prominent stressors in the MSNA literature are mental arithmetic and the Stroop test (Carter & Goldstein, 2015).

Given our previous findings (Dunn & Taylor, 2014) and observations in our lab regarding the timing of the plateau in the BP response to mental stress, the primary rate of rise analyses were performed using the first minute of the mental stressor tasks. This also appeared to be suitable for the current data in which BP tends to peak in the first minute. However, diastolic BP in negative responders (which turned out to be key to this study) did continue to rise throughout the 2min of mental arithmetic. In order to provide a more comprehensive review of this new approach, analyses were therefore performed using the first 30s and the full 2‐min stressor task.

For the 1‐min analysis the rate of rise was the clearest and most consistent difference between the positive and negative responders, i.e. significant for both stressors and for both classifications of responders (MSNA burst frequency and total MSNA), bar the Stroop test with total MSNA, which neared significance (P=0.06). With the 30‐s analysis, the difference in the rate of rise in diastolic BP between groups did not reach statistical significance, although there was evidence to suggest larger increases in BP in negative responders in this time period. For the 2‐min analysis, the rate of rise in systolic BP during mental arithmetic was significantly greater in negative responders, likely to be due to the lateness of the peak in systolic BP in the positive responders which, on average, occurred in the second minute. Trends for a greater rate of rise in diastolic BP did not reach significance. These differences may be explained by the timing of the peaks in BP and how adjusting the time period can affect which peak is captured by the analysis. During the first 30s BP was still in its primary rise for many individuals. Conversely, over the full 2‐min task there can be more than one peak. For instance, if a sharp rise in BP is followed by further fluctuations in pressure in which the final peak is eventually reached, selecting the largest BP and determining the rate of the rise can give the impression that the rise is slow when in fact the early response was rapid. The selection of the time period should reflect the research question. The primary aim of the current study was to examine the influence of the early peak in BP, hence focusing the analysis on the first minute of stress.

The current data do suggest that there is considerable variability in the timing of the BP peak during mental stress. In support of this, there is evidence in the literature indicating that blood pressure may continue to rise for 3min of mental stress or beyond (Anderson etal. 1991; Wallin etal. 1992; Middlekauff etal. 2001). This makes defining the most appropriate time period difficult and therefore future work with this approach might involve longer periods of stress in which specific criteria are developed for the identification of the peak or early BP response, depending on what is of interest.

Positive and negative responders to mental stress

Carter & Ray (2009) used the changes in MSNA burst frequency during mental stress to divide participants into groups of positive responders (increased MSNA by ≥∆3burstsmin⁻¹), negative responders (decreased MSNA by ≥∆3burstsmin⁻¹) and non‐responders. The study of 82 healthy males and females suggests that the typical distribution of MSNA responses in healthy, young populations may include large proportions of positive responders (n=40, 49%) and non‐responders (n=33, 40%), with smaller numbers of negative responders (n=9, 11%). This may be expected given that the majority of previous studies indicate either a significant mean increase (Kuniyoshi etal. 2003; Heindl etal. 2006; Scalco etal. 2009; Schwartz etal. 2011; Carter etal. 2013; Hering etal. 2013; Yang etal. 2013) or no change in MSNA with mental stress (Jones etal. 1996; Wilkinson etal. 1998; Wasmund etal. 2002; Carter etal. 2008; Kuipers etal. 2008), suggesting that these groups contained predominantly positive responders and/or non‐responders.

If the MSNA burst frequency thresholds used by Carter & Ray (2009) were applied to the current data, the sample would consist of six positive responders (29%), seven negative responders (33%) and seven non‐responders (33%) to mental arithmetic. For the Stroop test, there would be nine positive responders (43%), seven negative responders (33%) and five non‐responders (24%). The current study sample, albeit smaller than that of Carter & Ray (2009), therefore suggests a more even split into positive‐, negative‐ and non‐responders. When our analyses between positive and negative responders were repeated using the extremes, i.e. increases/decreases in MSNA burst frequency of ≥ 3burstsmin⁻¹ (Carter & Ray, 2009), the rate of rise in diastolic BP remained greater in negative responders but did not reach statistical significance (mental arithmetic, P=0.09; Stroop, P=0.08). Since dividing the current sample this way limited the statistical power for detecting significant differences between groups, the participants were classified as either positive or negative responders according to the direction of the change in MSNA. This meant that the two groups contained some individuals with changes of <3burstsmin^–1. If our approach for examining MSNA and blood pressure responses to mental stress were applied to a larger group of participants then positive, negative and non‐responder classifications may shed further light on the effects of the rate of rise in blood pressure on MSNA during mental stress. The use of different methods of classifying responses may also be useful within the literature, and in the current study we have added to this with the use of the total MSNA for the grouping of participants. This ensures that changes in MSNA burst amplitude are also taken into account.

Future directions

Although the current findings suggest that the early response in blood pressure influences the direction of the change in MSNA, it is not yet known if these early responses are repeatable within subjects. However, recent evidence indicates that the MSNA response is reproducible within a single day and across visits separated by 1month (Fonkoue & Carter, 2015). If the early BP responsiveness influences the MSNA response, as the current data suggest, then we might expect these early responses in BP to also be consistent within subjects. Further research is required to confirm this.

It is possible that some of the variability in the responses to mental stress in the current study and others may be due to the perceived difficulty of the task between participants. However, if this were the case, it might be expected that performance or anxiety be correlated with the blood pressure or MSNA response. Such correlations did not exist in the current study. Adjusting the level of mental tasks is not as straightforward as with physical stressors such as handgrip exercise. However, a set‐up where the difficulty of the challenge is adjusted in real time relative to the individual's performance may be useful, so that the participant constantly performs below a stated ‘average’. This would not only make the task more stressful but might help to provide a form of indexing.

It is not known if the responses reported in the current study are subject to sex differences. Vascular transduction of MSNA is lower in young females than young males (Briant etal. 2016), which may manifest in a more delayed rise in blood pressure at the onset of mental stress, and thus greater sympathetic activation during the stressor. Furthermore, evidence suggests that autonomic support of blood pressure and baroreflex buffering is lower in young females (Christou etal. 2005). Therefore, it might be postulated that baroreflex suppression of MSNA during mental stress is reduced, and that a larger proportion of females present as positive responders.

Parallel increases in blood pressure and MSNA during physical stressors

During the cold‐pressor test, heart rate increases rapidly, while the slower elevations in MSNA during the task parallel those of blood pressure. Likewise, during static handgrip exercise the increase in blood pressure occurs in parallel with the increase in both heart rate and MSNA, whilst during post‐exercise ischaemia the increases in blood pressure are driven by increases in MSNA. These responses have been well described previously (Victor etal. 1987a,b; fa*gius etal. 1989; Sander etal. 2010), and the current findings suggest that they are robust and consistent amongst healthy young males. An increase in blood pressure and MSNA (and a resetting of the baroreflex) represents an appropriate response of the autonomic nervous system to physiological challenges, such as exercise, ensuring adequate blood pressure and flow to the relevant regions (Mark etal. 1985; Boulton etal. 2014).

Competing interests

The authors declare no conflict of interest.

Author contributions

All experiments were performed at Western Sydney University, Sydney, Australia. The study was conceived and designed by K.E., V.G.M., M.J.J. and C.E.T. The data were acquired by K.E., V.G.M., S.L.H. and C.E.T. Analysis was performed by K.E. and C.E.T. The data were interpreted by K.E., M.J.J. and C.E.T. The work was drafted by K.E. and C.E.T. and critically revised by V.G.M., S.L.H. and M.J.J. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed.

Funding

Funding was not received for this study.

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