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American Journal of Physiology - Heart and Circulatory Physiology logoLink to American Journal of Physiology - Heart and Circulatory Physiology
. 2011 Feb 25;300(5):H1788–H1793. doi: 10.1152/ajpheart.00942.2010

Attenuation of sympathetic baroreflex sensitivity during the onset of acute mental stress in humans

John J Durocher 1, Jenna C Klein 1, Jason R Carter 1,
PMCID: PMC3094089  PMID: 21357505

Abstract

Mental stress consistently induces a pressor response that is often accompanied by a paradoxical increase of muscle sympathetic nerve activity (MSNA). The purpose of the present study was to evaluate sympathetic baroreflex sensitivity (BRS) by examining the relations between spontaneous fluctuations of diastolic arterial pressure (DAP) and MSNA. We hypothesized that sympathetic BRS would be attenuated during mental stress. DAP and MSNA were recorded during 5 min of supine baseline, 5 min of mental stress, and 5 min of recovery in 32 young healthy adults. Burst incidence and area were determined for each cardiac cycle and placed into 3-mmHg DAP bins; the slopes between DAP and MSNA provided an index of sympathetic BRS. Correlations between DAP and MSNA were strong (>0.5) during baseline in 31 of 32 subjects, but we evaluated the change in slope only for those subjects maintaining a strong correlation during mental stress (16 subjects). During baseline, the relation between DAP and MSNA was negative when expressed as either burst incidence [slope = −1.95 ± 0.18 bursts·(100 beats)−1·mmHg−1; r = −0.86 ± 0.03] or total MSNA [slope = −438 ± 91 units·(beat)−1 mmHg−1; r = −0.76 ± 0.06]. During mental stress, the slope between burst incidence and DAP was significantly reduced [slope = −1.14 ± 0.12 bursts·(100 beats)−1·mmHg−1; r = −0.72 ± 0.03; P < 0.01], indicating attenuation of sympathetic BRS. A more detailed analysis revealed an attenuation of sympathetic BRS during the first 2 min of mental stress (P < 0.01) but no change during the final 3 min of mental stress (P = 0.25). The present study demonstrates that acute mental stress attenuates sympathetic BRS, which may partially contribute to sympathoexcitation during the mental stress-pressor response. However, this attenuation appears to be isolated to the onset of mental stress. Moreover, variable MSNA responses to mental stress do not appear to be directly related to sympathetic BRS.

Keywords: arterial blood pressure, autonomic regulation, burst incidence, heart rate, hypertension, muscle sympathetic nerve activity


the primary function of the sympathetic arterial baroreflex is to assist with the beat-to-beat regulation of arterial blood pressure. Increases in arterial blood pressure load the baroreceptors and typically decrease muscle sympathetic nerve activity (MSNA) to help return blood pressure to a normal level. However, the acute hypertensive response to mental stress in humans is often associated with a paradoxical increase in MSNA (3, 6). It has been suggested that mental stress may override and/or alter baroreflex control of sympathetic activity (1), yet the influence of mental stress on sympathetic baroreflex sensitivity (BRS) has not been determined.

Several autonomic stressors such as cold-pressor test (22), isometric handgrip (7), and lower-body negative pressure (20) consistently increase MSNA. In contrast, mental stress elicits a widely variable MSNA response that includes increases, decreases, or no change in MSNA (6). Despite the widely variable sympathetic response, mental stress elicits a remarkably consistent increase in arterial blood pressure. The underlying mechanisms for the disassociation between arterial blood pressure and MSNA during mental stress remain unclear, but it is possible that a reduction of sympathetic BRS may contribute. Recently, a reliable nonpharmacological methodology has emerged to allow the determination of sympathetic BRS during mental stress. Specifically, the relations between spontaneous fluctuations of diastolic arterial blood pressure (DAP) and MSNA can be analyzed in an approach that provides an accurate slope assessment of sympathetic BRS (5, 1114, 21).

Therefore, the primary purpose of this study is to determine sympathetic BRS during mental stress. We hypothesize that mental stress will attenuate sympathetic BRS as indicated by a decrease in the spontaneous DAP-MSNA slope. Such findings could provide mechanistic insight into the variable MSNA responses that occur during mental stress.

MATERIALS AND METHODS

Subjects.

This study examined 32 healthy adults (11 males, 21 females; age 24 ± 1 yr, height 169 ± 2 cm, weight 68 ± 2 kg, body mass index 24 ± 1 kg/m2). Most participants were from two ongoing studies (16 from a double-blind placebo controlled fish oil study and seven from a mental stress/heat-stress study), and nine subjects were from a recently completed study (4). In all cases mental stress was the first intervention of the study and before any type of treatment. All subjects were nonsmoking normotensives (systolic = 110 ± 2 mmHg, diastolic = 66 ± 1 mmHg) and had no history of diabetes, cardiovascular disease, or autonomic dysfunction. Subjects were instructed to abstain from exercise, caffeine, and alcohol for 12 h before laboratory testing. The Institutional Review Board of Michigan Technological University approved the experimental protocol, and all participants provided written informed consent.

Experimental design.

Our protocol included 5 min of supine rest (i.e., baseline), 5 min of mental stress, and a 5 min recovery. Heart rate (HR), MSNA, and beat-to-beat arterial blood pressure were recorded throughout the study. Immediately following mental stress, subjects provided a rating of perceived stress on a zero-to-four scale (2).

Mental stress.

Mental stress consisted of 5 min of serial subtraction. Subjects were randomly assigned the number 6 or 7 and were instructed to subtract that number from two- or three-digit numbers that were provided randomly every 5 to 10 s. Subtraction was performed as quickly as possible while other investigators provided distractions.

Measurements.

Multifiber recordings of MSNA were obtained by inserting a tungsten microelectrode into the common peroneal nerve of a resting leg. A reference electrode was inserted subcutaneously 2–3 cm from the recording electrode. Both electrodes were connected to a differential preamplifier and amplifier (total gain of 80,000) where the nerve signal was band-pass filtered (700–2,000 Hz) and integrated (time constant, 0.1) to obtain a mean voltage neurogram. Satisfactory recordings of MSNA were defined by spontaneous pulse synchronous bursts that increased during end-expiratory apnea and did not change during auditory stimulation (yelling and clapping).

Arterial blood pressure was measured using two techniques. Resting arterial blood pressure was measured three consecutive times (separated by approximately 1-min intervals) using an automated sphygmomanometer and reported as a mean value. Continuous measurements of beat-to-beat arterial blood pressure were recorded via Finometer (Finapres Medical Systems, Amsterdam, The Netherlands). The Finometer is a reliable tool for determining relative changes in arterial blood pressure, but it does not provide accurate absolute values. Thus the Finometer was used to determine precise changes in arterial blood pressure that occurred from baseline to mental stress, while the sphygmomanometer allowed us to obtain accurate absolute resting arterial blood pressures. Arterial blood pressures are expressed as systolic (SAP), DAP, and mean (MAP) arterial pressures. HR was recorded using a three-lead electrocardiogram. Quality microneurography recordings were obtained throughout the baseline, mental stress, and recovery periods in all 32 subjects. Due to slight shifts in neurograms during mental stress, total MSNA is reported for 26 subjects (Tables 1 and 2).

Table 1.

Mean values for heart rate, arterial blood pressure, and MSNA

Variable Base MS1 MS2 MS3 MS4 MS5 Rec
HR, beats/min
    High Corr (n = 16) 66 ± 2 89 ± 3* 86 ± 3* 85 ± 4* 86 ± 4* 86 ± 4* 65 ± 2
    Low Corr (n = 16) 62 ± 2 80 ± 3* 78 ± 3* 77 ± 2* 78 ± 2* 78 ± 2* 62 ± 2
SAP, mmHg
    High Corr (n = 16) 116 ± 4 123 ± 4* 130 ± 4* 130 ± 4* 129 ± 4* 130 ± 4* 122 ± 4*
    Low Corr (n = 16) 114 ± 3 119 ± 3* 127 ± 3* 127 ± 3* 125 ± 3* 125 ± 4* 114 ± 3
DAP, mmHg
    High Corr (n = 16) 66 ± 3 73 ± 3* 77 ± 3* 77 ± 3* 77 ± 3* 77 ± 3* 68 ± 3*
    Low Corr (n = 16) 63 ± 3 69 ± 2* 74 ± 3* 74 ± 2* 73 ± 2* 74 ± 2* 65 ± 2
MAP, mmHg
    High Corr (n = 16) 84 ± 3 91 ± 3* 96 ± 3* 96 ± 3* 95 ± 3* 96 ± 3* 87 ± 3*
    Low Corr (n = 16) 81 ± 3 87 ± 3* 93 ± 3* 93 ± 3* 92 ± 3* 93 ± 3* 82 ± 3
MSNA, bursts/min
    High Corr (n = 16) 11 ± 2 15 ± 2* 16 ± 2* 16 ± 2* 17 ± 2* 17 ± 2* 16 ± 2*
    Low Corr (n = 16) 12 ± 2 13 ± 3 14 ± 3 18 ± 3* 16 ± 2* 15 ± 2 17 ± 2*
MSNA, bursts/100 hb
    High Corr (n = 16) 17 ± 2 17 ± 3 19 ± 3 19 ± 3 21 ± 3 20 ± 2 26 ± 4*
    Low Corr (n = 16) 20 ± 4 18 ± 4 20 ± 4 24 ± 4 22 ± 3 20 ± 3 28 ± 3*
Total MSNA, arbitrary units
    High Corr (n = 12) 595 ± 120 1307 ± 312* 1253 ± 326* 1140 ± 231* 1156 ± 270* 1080 ± 198* 831 ± 188*
    Low Corr (n = 14) 427 ± 70 534 ± 83 593 ± 116 758 ± 141* 748 ± 124* 679 ± 95* 546 ± 84

Values are means ± SE. Base, baseline; MS1-MS5, minutes 1–5 of mental stress; Rec, recovery; HR, heart rate; Corr, correlation; SAP, systolic arterial pressure; DAP, diastolic arterial pressure; MAP, mean arterial blood pressure; MSNA, muscle sympathetic nerve activity; hb, heart beats.

*

Significantly different than baseline (P < 0.05). Time x group interactions were not significant for all variables (all, P > 0.05), but the time x group for total MSNA (P = 0.06) approached significance.

Table 2.

Changes in heart rate, arterial blood pressure, and MSNA during mental stress

Variable All (n = 32) High Corr (n = 16) Low Corr (n = 16)
ΔHR, beats/min 18 ± 2* 20 ± 2* 16 ± 2*
ΔSAP, mmHg 12 ± 1* 12 ± 2* 11 ± 2*
ΔDAP, mmHg 10 ± 1* 10 ± 1* 9 ± 1*
ΔMAP, mmHg 11 ± 1* 11 ± 2* 11 ± 2*
ΔMSNA, bursts/min 4 ± 1* 5 ± 1* 3 ± 1*
ΔMSNA, bursts/ 100 hb 1 ± 1 2 ± 2 1 ± 2
ΔTotal MSNA, au 399 ± 95* 590 ± 132* 235 ± 122*

Values are mean ± SE; High Corr, subjects with DAP-MSNA correlations ≥0.5 (5 males, 11 females); Low Corr, subjects with DAP-MSNA correlations <0.5 (6 males, 10 females). ΔTotal MSNA includes 26 subjects (12 High Corr and 14 Low Corr). au, Arbitrary units.

*

Significantly different than baseline (P < 0.05).

Data analysis.

Data were imported and analyzed in the WinCPRS software program (Absolute Aliens, Turku, Finland). R-waves were detected and marked in the time series. Bursts of MSNA were automatically detected on the basis of amplitude using a signal-to-noise ratio of 3:1 within a 0.5-s search window centered on an expected 1.3-s burst peak latency from the previous R-wave. Potential bursts were displayed and edited by one trained investigator. The average area of the bursts occurring during baseline was normalized to a mean value of 10. MSNA was expressed as bursts per minute, bursts per 100 heart beats (burst incidence), and total burst activity (i.e., the sum of the normalized burst areas). HR, blood pressure, and MSNA are reported as 5-min averages during baseline and recovery, while responses to mental stress are reported minute by minute (Table 1).

Sympathetic BRS was determined by examining the relations between spontaneous fluctuations in DAP and MSNA (14, 21). This analysis has been described in detail previously (5, 13). In summary, DAP for each cardiac cycle was grouped into 3-mmHg intervals (bins) during baseline, mental stress, and recovery. Burst incidence and total MSNA for each DAP bin were calculated and plotted against the corresponding DAP (Fig. 2). The slopes of these relationships were evaluated with linear-regression analysis. All linear-regression analyses were weighted for the number of cardiac cycles within each DAP bin, and a minimum r value of 0.5 was used as the criteria for accepting slopes (14). Fifty percent of the subjects demonstrated a high correlation (≥0.5) for the burst incidence and/or total activity DAP-MSNA slopes during both baseline and mental stress. Baseline, mental stress, and recovery linear-regression slopes were determined from 5 min of data. In addition, slopes were determined separately for the first 2 min of mental stress while blood pressure progressively increased, and for the last 3 min when blood pressure reached a plateau.

Fig. 2.

Fig. 2.

Representative baroreflex-sensitivity slopes from 1 subject during baseline and mental stress. Slopes became less negative during mental stress, when the relations between diastolic arterial pressure (DAP) and MSNA are evaluated with MSNA as burst incidence (bursts per 100 heart beats), indicating a reduction in baroreflex sensitivity. No change occurs in slope from baseline to mental stress when examining the relations between total MSNA and DAP.

Statistical analysis.

All data were analyzed statistically using commercial software (SPSS 15.0; SPSS, Chicago, IL). A one-way repeated-measures ANOVA was utilized to determine whether changes in MSNA, SAP, DAP, MAP, HR, and DAP-MSNA slopes occurred during each intervention (baseline, mental stress, and recovery). A DAP-MSNA slope analysis was performed for all 32 subjects, but only those subjects with negative slopes and a correlation of ≥0.5 during baseline and mental stress were statistically evaluated with respect to the change in DAP-MSNA slope. Pearson correlations were utilized to probe for relationships between DAP-MSNA slopes and changes in MSNA burst frequency, HR, and blood pressure. Means were considered significantly different when P < 0.05. Results are expressed as mean ± SE.

RESULTS

Mean values for HR, arterial blood pressure, and MSNA are found in Table 1 for all 32 subjects. Data are separated into high and low DAP-MSNA correlation groups. HR, blood pressure, and MSNA expressed as bursts/minute and total MSNA increased significantly during mental stress. The neural and cardiovascular responses to mental stress were similar for both groups (no significant time × group interactions). However, the total MSNA response appears to be blunted in the low-correlation group (time × group interaction; P = 0.06). During recovery, all indices of MSNA remained elevated with the exception of total MSNA in the low-correlation subjects. Representative tracings of blood pressure and MSNA during baseline and mental stress are shown in Fig. 1.

Fig. 1.

Fig. 1.

Representative arterial blood pressure (BP) and muscle sympathetic nerve activity (MSNA) recordings from 1 subject during baseline and mental stress.

Table 2 depicts the neural and cardiovascular responses to mental stress for all 32 subjects and also provides separate columns for the subjects with high (r ≥ 0.5; n = 16) and low (r < 0.5; n = 16) DAP-MSNA correlations. Increases in HR, blood pressure, and MSNA burst frequency during mental stress were similar for all subjects. Mental stress did not change MSNA burst incidence, whereas increases in total MSNA tended to be greater in the subjects with a high DAP-MSNA correlation than those with a low correlation (P = 0.06). Perceived stress levels during mental stress were similar in the high-correlation group (2.9 ± 0.2 arbitrary units) and the low-correlation group (2.7 ± 0.2 arbitrary units).

DAP-MSNA correlations were greater than or equal to 0.5 during baseline in 31 of 32 subjects, but 16 subjects demonstrated low DAP-MSNA correlation during mental stress. The strength of correlation does not appear to be dependent on the range of DAP, as increased DAP ranges from baseline to mental stress were similar in the high (20 ± 3 vs. 31 ± 3 mmHg) and low (22 ± 3 vs. 29 ± 2 mmHg) correlation groups, respectively (time, P < 0.01; time × group interaction, P = 0.61). Changes from baseline to mental stress for all subjects are included in Table 2.

Figure 2 demonstrates that the relationship between DAP and MSNA was negative during supine baseline when expressed as either burst incidence [slope = −1.95 ± 0.18 bursts·(100 beats)−1·mmHg−1; r = −0.86 ± 0.03; n = 15] or total MSNA [slope = −438 ± 91 units·(beat)−1·mmHg−1; r = −0.76 ± 0.06; n = 10]. During mental stress, the slope of the relation between burst incidence and DAP was significantly more positive [slope = −1.14 ± 0.12 bursts·(100 beats)−1·mmHg−1; r = −0.72 ± 0.03; P < 0.01], indicating an attenuation of sympathetic BRS. Mental stress did not alter the total MSNA slope [slope = −608 ± 118 units·(beat)−1·mmHg−1; r = −0.72 ± 0.03]. During recovery, both the DAP-MSNA burst incidence slope [−1.53 ± 0.27 bursts·(100 beats)−1·mmHg−1; r = −0.75 ± 0.07] and the total DAP-MSNA slope [−527 ± 116 units·(beat)−1·mmHg−1; r = −0.81 ± 0.08] were similar to baseline values. Because DAP gradually increased throughout minutes 1–2 and then reached a steady-state in minutes 3–5, we examined sympathetic BRS during these separate times (Fig. 3). DAP-MSNA burst incidence slope was significantly reduced in the first 2 min of mental stress (slope = −0.99 ± 0.15; P < 0.01), but not during minutes 3–5 (slope = −1.74 ± 0.20; P = 0.25). Total MSNA slopes were not altered during either portion of mental stress.

Fig. 3.

Fig. 3.

Mean slopes and individual slopes between DAP and MSNA. The slope between DAP and MSNA becomes significantly less negative during mental stress when MSNA is reported as burst incidence during the first 2 min of mental stress (MS 1–2; top). However, the DAP-MSNA burst incidence slope remains unchanged during minutes 3 to 5 of mental stress (MS 3–5; bottom). *P < 0.01 from baseline.

Figure 4 demonstrates that mental stress elicited a variable MSNA response, yet this variability was not related to changes in sympathetic BRS. Specifically, changes in MSNA burst frequency were not correlated to baseline spontaneous DAP-MSNA burst incidence slopes (r = −0.17; P = 0.35) or to the change in DAP-MSNA burst incidence slopes from baseline to mental stress (r = 0.17; P = 0.53). No relationship existed between baseline DAP-MSNA-burst-incidence slope and change in HR, blood pressure, or MSNA during mental stress (r < 0.22 for all). Finally, changes in DAP-MSNA burst incidence slopes were not correlated to changes in SAP, MAP, or DAP (r < 0.22 for all) during mental stress.

Fig. 4.

Fig. 4.

Relations between changes in MSNA during mental stress and sympathetic baroreflex sensitivities at rest (top) and mental stress (bottom). No correlation existed between changes in MSNA burst frequency during mental stress and baseline DAP-MSNA burst incidence slope (top; n = 31). Similarly, changes in MSNA burst frequency and changes in DAP-MSNA burst incidence slope during mental stress were not correlated (bottom; n = 15).

DISCUSSION

The present study is the first to examine sympathetic BRS during mental stress. Our results provide four new findings. First, sympathetic BRS was attenuated during mental stress when expressed as DAP-MSNA burst incidence but not when expressed as total activity. Closer analysis revealed that this attenuation was isolated to the first 2 min of mental stress when blood pressure rises and unaltered during minutes 3 to 5 when the stress-induced increases of blood pressure plateau. Second, changes in MSNA during mental stress were not correlated to sympathetic BRS. Third, increases in total MSNA tended to be greater (P = 0.06) in subjects with a high DAP-MSNA correlation than those with a low correlation. Finally, half of our subjects demonstrated unacceptable DAP-MSNA correlations during mental stress (r < 0.5), indicating a potential disruption of sympathetic BRS. Collectively, our results demonstrate that mental stress attenuates and/or disrupts sympathetic BRS despite a widely variable MSNA response, suggesting that the well-documented MSNA variability during mental stress is not attributable to altered sympathetic baroreflex function.

Keller et al. (13) recently reported enhanced sympathetic BRS during heat stress compared with normothermic conditions using the spontaneous DAP-MSNA burst incidence-slope analysis. The authors suggest that the increase in sympathetic BRS may help protect against reductions in arterial blood pressure that might occur during heat stress, thus contributing positively to orthostatic tolerance (13). The present study demonstrated an attenuation of sympathetic BRS during mental stress when expressed as DAP-MSNA burst incidence slope. This attenuation may contribute to the concurrent increases in blood pressure and MSNA during mental stress. However, we did not find a direct correlation between changes in sympathetic BRS and blood pressure during mental stress, which would suggest that multiple mechanisms likely contribute to the concurrent increases. Our findings demonstrate no change in DAP-MSNA total slope from baseline to mental stress, which is consistent with that of Keller et al. (13), who reported no change in DAP-MSNA total slope during heat stress. Taken in conjunction with Keller et al. (13), our findings support the concept put forth by Kienbaum et al. (14) that baroreflex control of MSNA strength and incidence are not the same.

When assessing sympathetic BRS, the modified Oxford technique is considered the “gold standard” (12, 18, 19). Recently, the spontaneous DAP-MSNA burst incidence slope method used in the present study has been validated as a robust nonpharmacological alternative to the modified Oxford (12). Moreover, the modified Oxford technique alters arterial blood pressure pharmacologically with use of vasoactive drugs rather than tracking spontaneous variations in blood pressure. Mental stress elicits nonpharmacological, centrally induced increases in DAP, making the spontaneous DAP-MSNA slope analysis a practical method for examining sympathetic BRS during mental stress.

A recent study from our laboratory highlights the tremendous MSNA variability during mental stress by classifying subjects into responders, nonresponders, and negative responders on the basis of their change in MSNA burst frequency from baseline to mental stress (6). The present investigation once again demonstrated this wide variability, and Fig. 4 shows that changes in MSNA burst frequency during mental stress are not correlated to sympathetic BRS. Thus attenuation of BRS does not appear to be the mechanism for the variable MSNA responses to mental stress. It is likely that central command overrides baroreceptor regulation of arterial blood pressure during mental stress.

Investigating MSNA variability and sympathetic BRS during mental stress has clinical relevance. Noll et al. (17) reported that mental stress elicits an increase of MSNA in offspring of hypertensive parents but not in offspring of normotensive parents. Furthermore, reductions in sympathetic BRS are linked to hypertension (23). At least 50% of patients with essential hypertension are believed to have neurogenic factors (8), and evidence is growing for the contributions of chronic mental stress to high blood pressure (9). Specifically, simultaneous firing of single sympathetic fibers seem to commonly appear during chronic stress and in patients with essential hypertension (9).

The present study measured multi-unit sympathetic fibers and did not attempt to measure activity from single fibers. However, our findings that individuals with low DAP-MSNA correlations demonstrated a blunted increase (P = 0.06) of total MSNA during mental stress compared with those with high correlations could offer some insight. Kienbaum et al. (14) discussed two possible explanations why some subjects have a low DAP-MSNA correlation: 1) it is caused by other central and reflex inputs overriding baroreceptor control, or 2) differential sympathetic burst strength (i.e., total MSNA) and occurrence might contribute. Interestingly, it appears that the individuals with high DAP-MSNA correlation in the present study override baroreceptor control of MSNA during mental stress as sympathetic BRS is attenuated. The low-correlation subjects in the present study demonstrated a blunted change in total MSNA during mental stress, whereas their burst frequency and burst incidence responses were similar to the high-correlation individuals, which would support the latter explanation. Evidence exists that burst strength and burst occurrence are regulated at two separate synapses of the central nervous system (13, 14). It is possible that individuals with high DAP-MSNA correlations utilize the burst strength pathway to a greater extent than individuals with low correlations. Another potential explanation is that high-correlation individuals increase simultaneous single-unit firing that contributes to an increase in multi-unit burst strength. Recent evidence suggests that single-unit salvos may contribute to multi-unit burst amplitude (9, 16).

The link between mental stress and hypertension is complex and can vary on an individual basis. Contrary to their expectations, Young et al. (24) found that individuals with high trait anxiety had lower blood pressure responses to arithmetic, whereas the level of state anxiety did not affect blood pressure responsiveness. These findings suggest that individuals prone to anxiety may be somewhat protected from drastic increases in arterial blood pressure during cognitive stress. However, the mechanism for the reduced blood-pressure reactivity to mental stress was not explored. Individuals with panic disorder have elevated anxiety levels and are reported to be at an increased risk for cardiovascular complications, but Lambert et al. (15) found that patients with panic disorder have improved sympathetic BRS. This provided mechanistic insight for reduced blood-pressure responses to stress in individuals with high trait anxiety and raises the possibility that improved baroreflex function can result from chronic stress. The present study reports that sympathetic BRS was reduced during acute mental stress in young, healthy subjects, which is likely a contributing factor to concurrent increases in blood pressure and MSNA.

Sixteen of our subjects demonstrated unacceptable DAP-MSNA correlation during mental stress (r < 0.5). Despite this poor DAP-MSNA correlation, MSNA increased significantly during mental stress. Thus, even though sympathetic BRS was not analyzed by the DAP-MSNA slope method in these subjects, they demonstrate similar hemodynamic and neural responses. Specifically, mental stress increased HR, blood pressure, and MSNA burst frequency, and these increases were similar in the low and high DAP-MSNA correlation subjects as shown in Table 2. Thus the 16 subjects who did not model well with our spontaneous DAP-MSNA slope analysis (i.e., low-correlation subjects) still provide valuable data and insight into sympathetic baroreflex function during mental stress.

We attempted to analyze sympathetic BRS minute by minute, but data analysis revealed unacceptable correlations (i.e., r <0.5) sporadically throughout the 5-min mental stress interval, thus precluding repeated-measures analysis. We attribute this to limited data points (i.e., too few MSNA bursts and/or limited DAP range) for meaningful slope analysis. As such, we examined the data more closely in search of a more appropriate interval. Evaluation of the minute-by-minute DAP demonstrated that DAP gradually increased during the first 2 min of mental stress, and then reached an elevated steady state (i.e., plateau) during minutes 3–5 (Table 1). Analysis of sympathetic BRS within these timeframes yielded strong correlations (i.e., r >0.5). Similar to the entire 5-min analysis, we observed an attenuation of sympathetic BRS (expressed as burst incidence) during minutes 1–2. In contrast, sympathetic BRS was not different during minutes 3–5 when steady-state DAP was reached. Thus our data suggest an attenuation of baroreflex-mediated sympathoinhibition at the onset of mental stress in young, healthy humans. These findings provide new insight into the potential mechanisms responsible for the concurrent rise of blood pressure and MSNA during mental stress.

In conclusion, mental stress attenuates or disrupts sympathetic BRS during the initial 2 min of stress when expressed as DAP-MSNA burst incidence, a method that has also been referred to as the “gating” mechanism (13). A decrease in sympathetic BRS during mental stress may contribute to sympathoexcitation during concurrent increases in DAP, but altered sympathetic BRS does not appear to be the primary mechanism for the inconsistent MSNA responses to mental stress. Determining the mechanisms responsible for the variable MSNA response to mental stress remains important because of its potential clinical implications (9, 10, 17).

GRANTS

This project was supported by grants from the Michigan Space Grant Consortium and National Institutes of Health (HL-088689 and HL-098676).

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the authors.

ACKNOWLEDGMENTS

The authors thank Christopher Schwartz, Sarah Stream, John Lawrence, and Huan Yang for technical assistance. They also thank all subjects for willingness to participate.

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