Sympathetic determinants of resting blood pressure in males and females.

Discharge of postganglionic muscle sympathetic nerve activity (MSNA) is related poorly to blood pressure (BP) in adults. Whether neural measurements beyond the prevailing level of MSNA can account for interindividual differences in BP remains unclear. The current study sought to evaluate the relative contributions of sympathetic-BP transduction and sympathetic baroreflex gain on resting BP in young adults. Data were analyzed from 191 (77 females) young adults (18-39 years) who underwent continuous measurement of beat-to-beat BP (finger photoplethysmography), heart rate (electrocardiography), and fibular nerve MSNA (microneurography). Linear regression analyses were computed to determine associations between sympathetic-BP transduction (signal-averaging) or sympathetic baroreflex gain (threshold technique) and resting BP, before and after controlling for age, body mass index, and MSNA burst frequency. K-mean clustering was used to explore sympathetic phenotypes of BP control and consequential influence on resting BP. Sympathetic-BP transduction was unrelated to BP in males or females (both R2 < 0.01; P > 0.67). Sympathetic baroreflex gain was positively associated with BP in males (R2 = 0.09, P < 0.01), but not in females (R2 < 0.01; P = 0.80), before and after controlling for age, body mass index, and MSNA burst frequency. K-means clustering identified a subset of participants with average resting MSNA, yet lower sympathetic-BP transduction and lower sympathetic baroreflex gain. This distinct subgroup presented with elevated BP in males (P < 0.02), but not in females (P = 0.10). Sympathetic-BP transduction is unrelated to resting BP, while the association between sympathetic baroreflex gain and resting BP in males reveals important sex differences in the sympathetic determination of resting BP.NEW & NOTEWORTHY In a sample of 191 normotensive young adults, we confirm that resting muscle sympathetic nerve activity is a poor predictor of resting blood pressure and now demonstrate that sympathetic baroreflex gain is associated with resting blood pressure in males but not females. In contrast, signal-averaged measures of sympathetic-blood pressure transduction are unrelated to resting blood pressure. These findings highlight sex differences in the neural regulation of blood pressure.

Limb-specific muscle sympathetic nerve activity responses to the cold pressor test.

Recent studies have demonstrated that muscle sympathetic nerve activity (MSNA) responses to isometric exercise differs between active and inactive limbs. Whether limb-dependent responses are characteristic of responses to the cold pressor test (CPT) remains to be established. Therefore, we tested the hypothesis that CPT-induced MSNA responses differ between affected and unaffected limbs such that MSNA in the affected lower limb is greater than MSNA responses in the contralateral lower limb and the upper limb. Integrated peroneal MSNA (microneurography) was measured in young healthy individuals (n = 10) at rest and during three separate 3-min CPTs: the microneurography foot, opposite foot, and opposite hand. Peak MSNA responses were extracted for further analysis, as well as corresponding hemodynamic outcomes including mean arterial pressure (MAP; Finometer). MSNA responses were greater when the microneurography foot was immersed in ice water than when the opposite foot was immersed (38 ± 18 vs 28 ± 16 bursts/100hb: P < 0.01). MSNA responses when the opposite hand was immersed were greater than both the microneurography foot (46 ± 22 vs 38 ± 18 bursts/100hb: P < 0.01) and opposite foot (46 ± 22 vs 28 ± 16 bursts/100hb: P ≤0.01). Likewise, MAP responses were greater during the hand CPT than the microneurography foot (99 ± 9 vs 96 ± 8 mmHg: P < 0.01) and opposite foot CPT (99 ± 9 vs 96 ± 9 mmHg: P < 0.01). These data indicate that (a) upper limbs and (b) immersed limbs elicit greater MSNA responses to the CPT than lower and/or non-immersed limbs.

Guidelines on the use of sex and gender in cardiovascular research.

In cardiovascular research, sex and gender have not typically been considered in research design and reporting until recently. This has resulted in clinical research findings from which not only all women, but also gender-diverse individuals have been excluded. The resulting dearth of data has led to a lack of sex- and gender-specific clinical guidelines and raises serious questions about evidence-based care. Basic research has also excluded considerations of sex. Including sex and/or gender as research variables not only has the potential to improve the health of society overall now, but it also provides a foundation of knowledge on which to build future advances. The goal of this guidelines article is to provide advice on best practices to include sex and gender considerations in study design, as well as data collection, analysis, and interpretation to optimally establish rigor and reproducibility needed to inform clinical decision-making and improve outcomes. In cardiovascular physiology, incorporating sex and gender is a necessary component when optimally designing and executing research plans. The guidelines serve as the first guidance on how to include sex and gender in cardiovascular research. We provide here a beginning path toward achieving this goal and improve the ability of the research community to interpret results through a sex and gender lens to enable comparison across studies and laboratories, resulting in better health for all.

Autonomic control of cerebral blood flow: fundamental comparisons between peripheral and cerebrovascular circulations in humans.

Understanding the contribution of the autonomic nervous system to cerebral blood flow (CBF) control is challenging, and interpretations are unclear. The identification of calcium channels and adrenoreceptors within cerebral vessels has led to common misconceptions that the function of these receptors and actions mirror those of the peripheral vasculature. This review outlines the fundamental differences and complex actions of cerebral autonomic activation compared with the peripheral circulation. Anatomical differences, including the closed nature of the cerebrovasculature, and differential adrenoreceptor subtypes, density, distribution and sensitivity, provide evidence that measures on peripheral sympathetic nerve activity cannot be extrapolated to the cerebrovasculature. Cerebral sympathetic nerve activity seems to act opposingly to the peripheral circulation, mediated at least in part by changes in intracranial pressure and cerebral blood volume. Additionally, heterogeneity in cerebral adrenoreceptor distribution highlights region-specific autonomic regulation of CBF. Compensatory chemo- and autoregulatory responses throughout the cerebral circulation, and interactions with parasympathetic nerve activity are unique features to the cerebral circulation. This crosstalk between sympathetic and parasympathetic reflexes acts to ensure adequate perfusion of CBF to rising and falling perfusion pressures, optimizing delivery of oxygen and nutrients to the brain, while attempting to maintain blood volume and intracranial pressure. Herein, we highlight the distinct similarities and differences between autonomic control of cerebral and peripheral blood flow, and the regional specificity of sympathetic and parasympathetic regulation within the cerebrovasculature. Future research directions are outlined with the goal to further our understanding of autonomic control of CBF in humans.

Academic mothers, professional identity and COVID-19: Feminist reflections on career cycles, progression and practice.

Based on a collection of auto-ethnographic narratives that reflect our experiences as academic mothers at an Australian university, this paper seeks to illustrate the impact of COVID-19 on our career cycles in order to explore alternative feminist models of progression and practice in Higher Education. Collectively, we span multiple disciplines, parenting profiles, and racial/ethnic backgrounds. Our narratives (initiated in 2019) explicate four focal points in our careers as a foundation for analyzing self-definitions of professional identity: pre- and post-maternity career break; and pre- and post-COVID-19 career. We have modeled this research on a collective feminist research practice that is generative and empowering in terms of self-reflective models of collaborative research. Considering this practice and these narratives, we argue for a de-centering of masculinized career cycle patterns and progression pathways both now and beyond COVID-19. This represents both a challenge to neo-liberal norms of academic productivity, as well as a call to radically enhance institutional gender equality policies and practice.

The Role of Central Command in the Increase in Muscle Sympathetic Nerve Activity to Contracting Muscle During High Intensity Isometric Exercise.

We previously demonstrated that muscle sympathetic nerve activity (MSNA) increases to contracting muscle as well as to non-contracting muscle, but this was only assessed during isometric exercise at ∼10% of maximum voluntary contraction (MVC). Given that high-intensity isometric contractions will release more metabolites, we tested the hypothesis that the metaboreflex is expressed in the contracting muscle during high-intensity but not low-intensity exercise. MSNA was recorded continuously via a tungsten microelectrode inserted percutaneously into the right common peroneal nerve in 12 participants, performing isometric dorsiflexion of the right ankle at 10, 20, 30, 40, and 50% MVC for 2 min. Contractions were immediately followed by 6 min of post-exercise ischemia (PEI); 6 min of recovery separated contractions. Cross-correlation analysis was performed between the negative-going sympathetic spikes of the raw neurogram and the ECG. MSNA increased as contraction intensity increased, reaching mean values (± SD) of 207 ± 210 spikes/min at 10% MVC (P = 0.04), 270 ± 189 spikes/min at 20% MVC (P < 0.01), 538 ± 329 spikes/min at 30% MVC (P < 0.01), 816 ± 551 spikes/min at 40% MVC (P < 0.01), and 1,097 ± 782 spikes/min at 50% MVC (P < 0.01). Mean arterial pressure also increased in an intensity-dependent manner from 76 ± 3 mmHg at rest to 90 ± 6 mmHg (P < 0.01) during contractions of 50% MVC. At all contraction intensities, blood pressure remained elevated during PEI, but MSNA returned to pre-contraction levels, indicating that the metaboreflex does not contribute to the increase in MSNA to contracting muscle even at these high contraction intensities.

Sex differences in vascular transduction of sympathetic nerve activity.

PURPOSE: Sympathetic vasoconstriction plays a major role in the beat-to-beat control of blood pressure. To be effective and thus avoid dangerously high or low blood pressures, this mechanism relies upon transduction of sympathetic nerve activity at the level of the vasculature. However, recent evidence suggests that considerable variability exists in beat-to-beat vascular transduction, particularly between the sexes. METHODS: We reviewed the methods available for quantifying beat-to-beat transduction of muscle sympathetic nerve activity (MSNA) and explored the recent evidence for sex differences in vascular transduction. We paid specific attention to relationships between vascular transduction and factors such as resting levels of sympathetic nerve activity and baroreflex sensitivity. RESULTS: There are two dominant methods now available for the quantification of beat-to-beat transduction of muscle sympathetic nerve activity at rest. Whilst there is some evidence to suggest that young females exhibit lower levels of vascular transduction, results vary depending on the method used and the direction of change in MSNA. Evidence suggests that compensatory relationships may exist between key components of neurovascular control, such as vascular transduction and resting levels of MSNA. Also consistent is the presence of such relationships in young males but not young females. CONCLUSION: The lack of significant relationships in young females may reflect the influence of vasodilator mechanisms that counteract sympathetic vasoconstriction. The assessment of vascular transduction following MSNA bursts and non-bursts in males and females, both young and older, may help to gain a mechanistic understanding of the prevalence of hypotensive and hypertensive disorders across the lifespan.

Sympathetic baroreflex sensitivity is inversely related to vascular transduction in men but not women.

Sympathetic baroreflex sensitivity (BRS) is a measure of how effectively the baroreflex buffers beat-to-beat changes in blood pressure through the modulation of muscle sympathetic nerve activity (MSNA). However, current methods of assessment do not take into account the transduction of sympathetic nerve activity at the level of the vasculature, which is known to vary between individuals. In this study we tested the hypothesis that there is an inverse relationship between sympathetic BRS and vascular transduction. In 38 (18 men) healthy adults, continuous measurements of blood pressure, MSNA and superficial femoral artery diameter and blood flow (Doppler ultrasound) were recorded during 10 min of rest. Spontaneous sympathetic BRS was quantified as the relationship between diastolic pressure and MSNA burst incidence. Vascular transduction was quantified by plotting the changes in leg vascular conductance for 10 cardiac cycles following each burst of MSNA, and taking the nadir. In men, sympathetic BRS was inversely related to vascular transduction (r = -0.49; P = 0.04). However, this relationship was not present in women (r = -0.17; P = 0.47). To conclude, an interaction exists between sympathetic BRS and vascular transduction in healthy men, such that men with high sympathetic BRS have low vascular transduction and vice versa. This may be to ensure that blood pressure is regulated effectively, although further research is needed to explore what mechanisms are involved and examine why this relationship was not apparent in women.NEW & NOTEWORTHY Evidence suggests that compensatory interactions exist between factors involved in cardiovascular control. This study was the first to demonstrate an inverse relationship between sympathetic BRS and beat-to-beat vascular transduction. Those with low sympathetic BRS had high vascular transduction and vice versa. However, this interaction was present in young men but not women.

A Comparison of Muscle Sympathetic Nerve Activity to Non-contracting Muscle During Isometric Exercise in the Upper and Lower Limbs.

Previous research indicates that greater sympathetic vasoconstrictor drive to skeletal muscle occurs during isometric upper limb exercise compared to lower limb exercise. However, potential disparity between blood flow and metaboreflex activation in contracting upper and lower limbs could contribute to the augmented sympathetic response during upper limb exercise. Therefore, the aim of this study was to examine MSNA responses during ankle dorsiflexion and handgrip exercise under ischaemic conditions, in order to standardize the conditions in terms of perfusion and metaboreflex activation. Eight healthy male subjects performed 4-min contractions of ischaemic isometric handgrip and ankle dorsiflexion at ∼10% maximal voluntary contraction, followed by 6 min of post-exercise ischaemia. MSNA was recorded continuously by microneurography of the common peroneal nerve of the non-contracting leg and quantified from negative-going sympathetic spikes in the neurogram, synchronized with the cardiac cycle. The time-course of MSNA exhibited parallel increases during exercise of the upper and lower limbs, rising throughout the contraction to peak at 4 min. This represented an increase of 100% relative to resting levels for handgrip exercise (66 ± 24 vs. 33 ± 7 spikes/min at rest) and 103% for dorsiflexion (63 ± 25 vs. 31 ± 8 spikes/min at rest; P < 0.01). In both conditions MSNA remained elevated during post-exercise ischaemia and returned to pre-contraction levels during recovery. These findings demonstrate that that the MSNA response to metaboreflex activation is similar for upper and lower limb exercise when perfusion is controlled for.

Central command increases muscle sympathetic nerve activity more to contracting than noncontracting muscle during rhythmic isotonic leg exercise.

We have previously shown that the increase in muscle sympathetic nerve activity (MSNA) to contracting muscle during sustained isometric exercise is due primarily to central command and that contracting muscle does not express a metaboreceptor-driven increase in MSNA. Here we tested the hypothesis that MSNA increases to the contracting muscle also during rhythmic isotonic exercise, in which muscle metabolites will not accumulate because the contraction is performed without external load. MSNA was recorded from the common peroneal nerve in 10 participants, and negative-going sympathetic spikes were extracted during 50 cycles of sinusoidal (0.15 Hz) isotonic dorsiflexions of the ipsilateral or contralateral ankle. Electromyographic activity (EMG) was recorded from the tibialis anterior muscle on both sides. Cross-correlation analysis between MSNA and EMG revealed a marked cyclic modulation of MSNA to the contracting (ipsilateral) muscle. This modulation, in which MSNA increased during the contraction phase, was three times greater than that to the noncontracting muscle (modulation index = 27.4 ± 3.2% vs. 9.2 ± 1.5%; P < 0.002). There were no differences in either the intensity or the magnitude of modulation of EMG during ipsilateral and contralateral contractions. We conclude that central command increases MSNA to the contracting muscle during rhythmic isotonic exercise. NEW & NOTEWORTHY Muscle sympathetic nerve activity (MSNA) increases to contracting muscle during isometric exercise, but whether this occurs during rhythmic isotonic exercise is unknown. We recorded MSNA to the pretibial flexors during cyclic dorsiflexion of the ipsilateral or contralateral ankle. MSNA showed a cyclic increase during the contraction phase that was significantly higher to the contracting than the noncontracting muscle, supporting central command as the primary mechanism responsible for increasing MSNA.

Blood pressure reactivity at onset of mental stress determines sympathetic vascular response in young adults.

We have previously shown in young males that the rate of rise in blood pressure (BP) at the onset of mental stress determines whether or not muscle sympathetic nerve activity (MSNA) has a role in driving the pressor response. The aim of this study was to investigate these interactions in young females. BP and MSNA were recorded continuously in 19 females and 21 males during 2-min mental stressors (mental arithmetic and Stroop test). Physical stressor tasks (cold pressor, handgrip exercise, postexercise ischemia) were also performed. During the first minute of mental arithmetic, the rate of rise in mean arterial pressure (MAP) was significantly greater in negative responders (mean decrease in MSNA) compared with positive responders (mean increase in MSNA) in both males (1.9 ± 0.7 vs. 0.7 ± 0.3 mmHg/sec) and females (1.0 ± 0.3 vs. 0.5 ± 0.2 mmHg/sec). For the Stroop test, there was no significant difference in the rate of the rise in BP between positive and negative responders (P > 0.05). However, peak changes in MAP were significantly greater in negative responders compared with positive responders in both males (22 ± 6 vs. 13 ± 3 mmHg) and females (12 ± 2 vs. 6 ± 1 mmHg). Sympathetic baroreflex sensitivity was greater in negative responders and may contribute to the fall in MSNA experienced by these individuals during mental stress. During physical stressors there were consistent increases in BP and MSNA in males and females. The findings suggest that, in both males and females, BP reactivity at the onset of mental stress dictates whether or not there is an increase or decrease in MSNA.

The Stability and Repeatability of Spontaneous Sympathetic Baroreflex Sensitivity in Healthy Young Individuals.

Spontaneous sympathetic baroreflex sensitivity (BRS) is a valuable tool for assessing how well the baroreflex buffers beat-to-beat changes in blood pressure. However, there has yet to be a study involving appropriate statistical tests to examine the stability of sympathetic BRS within an experimental session and the repeatability between separate sessions. The aim of this study was to use intra-class correlations, ordinary least products regression, and Bland-Altman analyses to examine the stability and repeatability of spontaneous sympathetic BRS assessment. In addition, the influence of recording duration on values of BRS was assessed. In eighty-four healthy young individuals (49 males, 35 females), continuous measurements of blood pressure, heart rate and muscle sympathetic nerve activity (MSNA) were recorded for 10 min. In a subgroup of 13 participants (11 male, 2 female) the measurements were repeated on a separate day. Sympathetic BRS was quantified using MSNA burst incidence (BRSinc) and total MSNA (BRStotal) for the first 5-min period, the second 5-min period, and a 2-min segment taken from the second 5-min period. Intra-class correlation coefficients indicated moderate stability in sympathetic BRSinc and BRStotal between the first and second 5-min periods in males (BRSincr = 0.63, BRStotalr = 0.78) and females (BRSincr = 0.61, BRStotalr = 0.47) with no proportional bias, but with fixed bias for BRSinc in females. When comparing the first 5-min with the 2-min period (n = 76), the intra-class correlation coefficient indicated poor to moderate repeatability in sympathetic BRSinc and BRStotal for males (BRSincr = -0.01, BRStotalr = 0.70) and females (BRSincr = 0.46, BRStotalr = 0.39). However, Bland-Altman analysis revealed a fixed bias for BRStotal in males and proportional bias for BRStotal in females, with lower BRS values for 5-min recordings. In the subgroup, intra-class correlations indicated moderate repeatability for measures of BRSinc (9 male, 2 female, r = 0.63) and BRStotal (6 male, 2 female, r = 0.68) assessed using 5-min periods recorded on separate days. However, Bland-Altman analysis indicated proportional bias for BRSinc and fixed bias for BRStotal. In conclusion, measures of spontaneous sympathetic BRS are moderately stable and repeatable within and between testing sessions in healthy young adults, provided that the same length of recording is used when making comparisons.

The metaboreflex does not contribute to the increase in muscle sympathetic nerve activity to contracting muscle during static exercise in humans.

KEY POINTS: It is not clear how sympathetic activity to contracting muscle is controlled. We recorded muscle sympathetic nerve activity (MSNA) to the ipsilateral tibialis anterior muscle during 4 min of isometric dorsiflexion of the ankle and 6 min of post-exercise ischaemia, which was repeated contralaterally. MSNA to the contracting muscle increased within 1 min of static exercise and returned to pre-contraction levels at the end. Unlike the increase in MSNA seen in the non-contracting muscle, post-exercise ischaemia had no effect on MSNA to the contracted muscle. We conclude that central command is the primary mechanism responsible for increasing MSNA to contracting muscle and also that the metaboreflex is not expressed in contracting muscle. ABSTRACT: Both central command and metaboreflex inputs from contracting muscles increase muscle sympathetic nerve activity (MSNA) to non-contracting muscle during sustained isometric exercise. We recently showed that MSNA to contracting muscle also increases in an intensity-dependent manner, although whether this can be sustained by the metaboreflex is unknown. MSNA was recorded from the left common peroneal nerve and individual spikes of MSNA extracted from the nerve signal. Eleven subjects performed a series of 4 min dorsiflexions of the left ankle at 10% of maximum voluntary contraction under three conditions: without ischaemia, with 6 min of post-exercise ischaemia, and with ischaemia during and after exercise; these were repeated in the right leg. Compared with pre-contraction values, MSNA to the contracting muscles increased and plateaued in the first minute of contraction (50 ± 18 vs. 34 ± 10 spikes min-1 , P = 0.01), returned to pre-contraction levels within 1 min of the contraction ending and was not influenced by ischaemia during or after contraction. Conversely, MSNA to the non-contracting muscles was not different from pre-contraction levels in the first minute of contraction (34 ± 9 vs. 32 ± 5 spikes min-1 , P = 0.48), whereas it increased each minute and was significantly greater by the second minute (44 ± 8 spikes min-1 , P = 0.01). Ischaemia augmented the MSNA response to contraction (63 ± 25 spikes min-1 after 4 min, P < 0.05) and post-exercise ischaemia (63 ± 27 spikes min-1 after 6 min, P < 0.01) for the non-contracting muscles only. These findings support our conclusion that the metaboreflex is not expressed in the contracting muscle during sustained static exercise.

Inter-individual Relationships between Sympathetic Arterial Baroreflex Function and Cerebral Perfusion Control in Healthy Males.

Maintenance of adequate cerebral perfusion during normal physiological challenges requires integration between cerebral blood flow (CBF) and systemic blood pressure control mechanisms. Previous studies have shown that cardiac baroreflex sensitivity (BRS) is inversely related to some measures of cerebral autoregulation. However, interactions between the sympathetic arterial baroreflex and cerebral perfusion control mechanisms have not been explored. To determine the nature and magnitude of these interactions we measured R-R interval, blood pressure, CBF velocity, and muscle sympathetic nerve activity (MSNA) in 11 healthy young males. Sympathetic BRS was estimated using modified Oxford method as the relationship between beat-to-beat diastolic blood pressure (DBP) and MSNA. Integrated control of CBF was quantified using transfer function analysis (TFA) metrics derived during rest and Tieck's autoregulatory index following bilateral thigh cuff deflation. Sympathetic BRS during modified Oxford trials was significantly related to autoregulatory index (r = 0.64, p = 0.03). Sympathetic BRS during spontaneous baseline was significantly related to transfer function gain (r = -0.74, p = 0.01). A more negative value for sympathetic BRS indicates more effective arterial baroreflex regulation, and a lower transfer function gain reflects greater cerebral autoregulation. Therefore, these findings indicate that males with attenuated CBF regulation have greater sympathetic BRS (and vice versa), consistent with compensatory interactions between blood pressure and cerebral perfusion control mechanisms.

Muscle sympathetic nerve activity peaks in the first trimester in healthy pregnancy: a longitudinal case study.

OBJECTIVE AND METHODS: Muscle sympathetic nerve activity and baroreflex sensitivity were examined at rest before, during (weeks 6, 11, 17, 22, 25, 33 and 36) and after a normotensive pregnancy. RESULTS: Muscle sympathetic nerve activity is elevated during pregnancy with a large peak in the first trimester (Δ17 bursts/min) and a secondary peak in the third trimester (Δ11 bursts/min). Cardiac baroreflex sensitivity peaked in the first trimester (10 vs. 6 ms/mmHg pre-pregnancy), whereas sympathetic baroreflex sensitivity was greater throughout. INTERPRETATION: The increase in sympathetic outflow early in pregnancy cannot be explained by a reduction in baroreflex sensitivity, while the secondary increase in burst frequency in the third trimester may, in part, be explained by the elevated heart rate.

Rate of rise in diastolic blood pressure influences vascular sympathetic response to mental stress.

KEY POINTS: 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. ABSTRACT: Research indicates that individuals may experience a rise (positive responders) or fall (negative responders) in muscle sympathetic nerve activity (MSNA) during mental stress. The aim was to examine the early blood pressure response to stress in positive and negative responders and thus its influence on the direction of change in MSNA. Blood pressure and MSNA were recorded continuously in 21 healthy young males during 2 min mental stressors (mental arithmetic, Stroop test) and physical stressors (cold pressor, handgrip exercise, post-exercise ischaemia). Participants were classified as negative or positive responders according to the direction of the mean change in MSNA during the stressor tasks. The peak changes, time of peak and rate of changes in blood pressure were compared between groups. During mental arithmetic negative responders experienced a significantly greater rate of rise in diastolic blood pressure in the first minute of the task (1.3 ± 0.5 mmHg s-1 ) compared with positive responders (0.4 ± 0.1 mmHg s-1 ; P = 0.03). Similar results were found for the Stroop test. Physical tasks elicited robust parallel increases in blood pressure and MSNA across participants. It is concluded that 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.