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

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.     

Influence of acute alcohol ingestion on sympathetic neural responses to orthostatic stress in humans

Acute alcohol consumption is reported to decrease mean arterial pressure (MAP) during orthostatic challenge, a response that may contribute to alcohol-mediated syncope. Muscle sympathetic nerve activity (MSNA) increases during orthostatic stress to help maintain MAP, yet the effects of alcohol on MSNA responses during orthostatic stress have not been determined. We hypothesized that alcohol ingestion would blunt arterial blood pressure and MSNA responses to lower body negative pressure (LBNP). MAP, MSNA, and heart rate (HR) were recorded during progressive LBNP (-5, -10, -15, -20, -30, and -40 mmHg; 3 min/stage) in 30 subjects (age 24 ± 1 yr). After an initial progressive LBNP (pretreatment), subjects consumed either alcohol (0.8 g ethanol/kg body mass; n = 15) or placebo (n = 15), and progressive LBNP was repeated (posttreatment). Alcohol increased resting HR (59 ± 2 to 65 ± 2 beats/min, P < 0.05), MSNA (13 ± 3 to 19 ± 4 bursts/min, P < 0.05), and MSNA burst latency (1,313 ± 16 to 1,350 ± 17 ms, P < 0.05) compared with placebo (group × treatment interactions, P < 0.05). During progressive LBNP, a pronounced decrease in MAP was observed after alcohol but not placebo (group × time × treatment, P < 0.05). In contrast, MSNA and HR increased during all LBNP protocols, but there were no differences between trials or groups. However, alcohol altered MSNA burst latency response to progressive LBNP. In conclusion, the lack of MSNA adjustment to a larger drop in arterial blood pressure during progressive LBNP, coupled with altered sympathetic burst latency responses, suggests that alcohol blunts MSNA responses to orthostatic stress.     

Sympathetic neural responses to 24-hour sleep deprivation in humans: sex differences

Sleep deprivation has been linked to hypertension, and recent evidence suggests that associations between short sleep duration and hypertension are stronger in women. In the present study we hypothesized that 24 h of total sleep deprivation (TSD) would elicit an augmented pressor and sympathetic neural response in women compared with men. Resting heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were measured in 30 healthy subjects (age, 22 ± 1; 15 men and 15 women). Relations between spontaneous fluctuations of diastolic arterial pressure and MSNA were used to assess sympathetic baroreflex function. Subjects were studied twice, once after normal sleep and once after TSD (randomized, crossover design). TSD elicited similar increases in systolic, diastolic, and mean BP in men and women (time, P < 0.05; time × sex, P > 0.05). TSD reduced MSNA in men (25 ± 2 to 16 ± 3 bursts/100 heart beats; P = 0.02), but not women. TSD did not alter spontaneous sympathetic or cardiovagal baroreflex sensitivities in either sex. However, TSD shifted the spontaneous sympathetic baroreflex operating point downward and rightward in men only. TSD reduced testosterone in men, and these changes were correlated to changes in resting MSNA (r = 0.59; P = 0.04). Resting HR, respiratory rate, and estradiol were not altered by TSD in either sex. In conclusion, TSD-induced hypertension occurs in both sexes, but only men demonstrate altered resting MSNA. The sex differences in MSNA are associated with sex differences in sympathetic baroreflex function (i.e., operating point) and testosterone. These findings may help explain why associations between sleep deprivation and hypertension appear to be sex dependent.     

Sex differences in the modulation of vasomotor sympathetic outflow during static handgrip exercise in healthy young humans

Sex differences in sympathetic neural control during static exercise in humans are few and the findings are inconsistent. We hypothesized women would have an attenuated vasomotor sympathetic response to static exercise, which would be further reduced during the high sex hormone [midluteal (ML)] vs. the low hormone phase [early follicular (EF)]. We measured heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) in 11 women and 10 men during a cold pressor test (CPT) and static handgrip to fatigue with 2 min of postexercise circulatory arrest (PECA). HR increased during handgrip, reached its peak at fatigue, and was comparable between sexes. BP increased during handgrip and PECA where men had larger increases from baseline. Mean ± SD MSNA burst frequency (BF) during handgrip and PECA was lower in women (EF, P < 0.05), as was ΔMSNA-BF smaller (main effect, both P < 0.01). ΔTotal activity was higher in men at fatigue (EF: 632 ± 418 vs. ML: 598 ± 342 vs. men: 1,025 ± 416 a.u./min, P < 0.001 for EF and ML vs. men) and during PECA (EF: 354 ± 321 vs. ML: 341 ± 199 vs. men: 599 ± 327 a.u./min, P < 0.05 for EF and ML vs. men). During CPT, HR and MSNA responses were similar between sexes and hormone phases, confirming that central integration and the sympathetic efferent pathway was comparable between the sexes and across hormone phases. Women demonstrated a blunted metaboreflex, unaffected by sex hormones, which may be due to differences in muscle mass or fiber type and, therefore, metabolic stimulation of group IV afferents.     

Carotid baroreflex regulation of sympathetic nerve activity during dynamic exercise in humans

We sought to determine whether carotid baroreflex (CBR) control of muscle sympathetic nerve activity (MSNA) was altered during dynamic exercise. In five men and three women, 23.8 +/- 0.7 (SE) yr of age, CBR function was evaluated at rest and during 20 min of arm cycling at 50% peak O(2) uptake using 5-s periods of neck pressure and neck suction. From rest to steady-state arm cycling, mean arterial pressure (MAP) was significantly increased from 90.0 +/- 2.7 to 118.7 +/- 3.6 mmHg and MSNA burst frequency (microneurography at the peroneal nerve) was elevated by 51 +/- 14% (P < 0.01). However, despite the marked increases in MAP and MSNA during exercise, CBR-Delta%MSNA responses elicited by the application of various levels of neck pressure and neck suction ranging from +45 to -80 Torr were not significantly different from those at rest. Furthermore, estimated baroreflex sensitivity for the control of MSNA at rest was the same as during exercise (P = 0.74) across the range of neck chamber pressures. Thus CBR control of sympathetic nerve activity appears to be preserved during moderate-intensity dynamic exercise.     

Sex differences in hemodynamic and sympathetic neural firing patterns during orthostatic challenge in humans

Recent evidence suggests that young men and women may have different strategies for regulating arterial blood pressure, and the purpose of the present study was to determine if sex differences exist in diastolic arterial pressure (DAP) and muscle sympathetic nerve activity (MSNA) relations during simulated orthostatic stress. We hypothesized that young men would demonstrate stronger DAP-MSNA coherence and a greater percentage of "consecutive integrated bursts" during orthostatic stress. Fourteen men and 14 women (age 23 ± 1 yr) were examined at rest and during progressive lower body negative pressure (LBNP; -5 to -40 mmHg). Progressive LBNP did not alter mean arterial pressure (MAP) in either sex. Heart rate increased and stroke volume decreased to a greater extent during LBNP in women (interactions, P < 0.05). DAP-MSNA coherence was strong (i.e., r ≥ 0.5) at rest and increased throughout all LBNP stages in men. In contrast, DAP-MSNA coherence was lower in women, and responses to progressive LBNP were attenuated compared with men (time × sex, P = 0.029). Men demonstrated a higher percentage of consecutive bursts during all stages of LBNP (sex, P < 0.05), although the percentage of consecutive bursts increased similarly during progressive LBNP between sexes. In conclusion, men and women demonstrate different firing patterns of integrated MSNA during LBNP that appear to be related to differences in DAP oscillatory patterns. Men tend to have more consecutive bursts, which likely contribute to a stronger DAP-MSNA coherence. These findings may help explain why young women are more prone to orthostatic intolerance.     

Sympathetic adaptations to one-legged training.

The purpose of the present study was to determine the effect of leg exercise training on sympathetic nerve responses at rest and during dynamic exercise. Six men were trained by using high-intensity interval and prolonged continuous one-legged cycling 4 day/wk, 40 min/day, for 6 wk. Heart rate, mean arterial pressure (MAP), and muscle sympathetic nerve activity (MSNA; peroneal nerve) were measured during 3 min of upright dynamic one-legged knee extensions at 40 W before and after training. After training, peak oxygen uptake in the trained leg increased 19 +/- 2% (P < 0.01). At rest, heart rate decreased from 77 +/- 3 to 71 +/- 6 beats/min (P < 0.01) with no significant changes in MAP (91 +/- 7 to 91 +/- 11 mmHg) and MSNA (29 +/- 3 to 28 +/- 1 bursts/min). During exercise, both heart rate and MAP were lower after training (108 +/- 5 to 96 +/- 5 beats/min and 132 +/- 8 to 119 +/- 4 mmHg, respectively, during the third minute of exercise; P < 0.01). MSNA decreased similarly from rest during the first 2 min of exercise both before and after training. However, MSNA was significantly less during the third minute of exercise after training (32 +/- 2 to 22 +/- 3 bursts/min; P < 0.01). This training effect on MSNA remained when MSNA was expressed as bursts per 100 heartbeats. Responses to exercise in five untrained control subjects were not different at 0 and 6 wk. These results demonstrate that exercise training prolongs the decrease in MSNA during upright leg exercise and indicates that attenuation of MSNA to exercise reported with forearm training also occurs with leg training.     

Hemodynamics and brain blood flow during posture change in younger women and postmenopausal women compared with age-matched men

Increased incidence of orthostatic hypotension and presyncopal symptoms in young women could be related to hormonal factors that might be isolated by comparing cardiovascular and cerebrovascular responses to postural change in young and older men and women. Seven young women, 11 young men, 10 older women (>1 yr postmenopausal, no hormone therapy), and 9 older men participated in a supine-to-sit-to-stand test while measuring systemic hemodynamics, end-tidal Pco(2), and blood flow velocity of the middle cerebral artery (MCA). Women had a greater reduction in stroke volume index compared with age-matched men (change from supine to standing: young women: -22.9 ± 1.6 ml/m(2); young men: -14.4 ± 2.4 ml/m(2); older women: -17.4 ± 3.3 ml/m(2); older men: -13.8 ± 2.2 ml/m(2)). This was accompanied by offsetting changes in heart rate, particularly in young women, resulting in no age or sex differences in cardiac output index. Mean arterial pressure (MAP) was higher in older subjects and increased with movement to upright postures. Younger men and women had higher forearm vascular resistance that increased progressively in the upright posture compared with older men and women. There was no difference between sexes or ages in total peripheral resistance index. Women had higher MCA velocity, but both sexes had reduced MCA velocity while upright, which was a function of reduced blood pressure at the MCA and a significant reduction in end-tidal Pco(2). The reductions in stroke volume index suggested impaired venous return in women, but augmented responses of heart rate and forearm vascular resistance protected MAP in younger women. Overall, these results showed significant sex and age-related differences, but compensatory mechanisms preserved MAP and MCA velocity in young women.     

Effects of expiratory muscle work on muscle sympathetic nerve activity.

We hypothesized that contractions of the expiratory muscles carried out to the point of task failure would cause an increase in muscle sympathetic nerve activity (MSNA). We measured MSNA directly in six healthy men during resisted expiration (60% maximal expiratory pressure) leading to task failure with long [breathing frequency (f(b)) = 15 breaths/min; expiratory time (TE)/total respiratory cycle duration (TT) = 0.7] and short (f(b) = 30 breaths/min; TE/TT = 0.4) TE. Both of these types of expiratory muscle contractions elicited time-dependent increases in MSNA burst frequency that averaged +139 and +239%, respectively, above baseline at end exercise. The increased MSNA coincided with increases in mean arterial pressure (MAP) for both the long-TE (+28 +/- 6 mmHg) and short-TE (+22 +/- 14 mmHg) trials. Neither MSNA nor MAP changed when the breathing patterns and increased tidal volume of the task failure trials were mimicked without resistance or task failure. Furthermore, very high levels of expiratory motor output (95% maximal expiratory pressure; f(b) = 12 breaths/min; TE/TT = 0.35) and high rates of expiratory flow and expiratory muscle shortening without task failure (no resistance; f(b) = 45 breaths/min; TE/TT = 0.4; tidal volume = 1.9 x eupnea) had no effect on MSNA or MAP. Within-breath analysis of the short-expiration trials showed augmented MSNA at the onset of and throughout expiration that was consistent with an influence of high levels of central expiratory motor output. Thus high-intensity contractions of expiratory muscles to the point of task failure caused a time-dependent sympathoexcitation; these effects on MSNA were similar in their time dependency to those caused by high-intensity rhythmic contractions of the diaphragm and forearm muscles taken to the point of task failure. The evidence suggests that these effects are mediated primarily via a muscle metaboreflex with a minor, variable contribution from augmented central expiratory motor output.     

Baroreflex control of muscle sympathetic nerve activity as a mechanism for persistent sympathoexcitation following acute hypoxia in humans

This study tested the hypothesis that acute isocapnic hypoxia results in persistent resetting of the baroreflex to higher levels of muscle sympathetic nerve activity (MSNA), which outlasts the hypoxic stimulus. Cardiorespiratory measures were recorded in humans (26 ± 1 yr; n = 14; 3 women) during baseline, exposure to 20 min of isocapnic hypoxia, and for 5 min following termination of hypoxia. The spontaneous baroreflex threshold technique was used to determine the change in baroreflex function during and following 20 min of isocapnic hypoxia (oxyhemoglobin saturation = 80%). From the spontaneous baroreflex analysis, the linear regression between diastolic blood pressure (DBP) and sympathetic burst occurrence, the T50 (DBP with a 50% likelihood of a burst occurring), and DBP error signal (DBP minus the T50) provide indexes of baroreflex function. MSNA and DBP increased in hypoxia and remained elevated during posthypoxia relative to baseline (P < 0.05). The DBP error signal became progressively less negative (i.e., smaller difference between DBP and T50) in the hypoxia and posthypoxia periods (baseline: -3.9 ± 0.8 mmHg; hypoxia: -1.4 ± 0.6 mmHg; posthypoxia: 0.2 ± 0.6 mmHg; P < 0.05). Hypoxia caused no change in the slope of the baroreflex stimulus-response curve; however, there was a shift toward higher pressures that favored elevations in MSNA, which persisted posthypoxia. Our results indicate that there is a resetting of the baroreflex in hypoxia that outlasts the stimulus and provide further explanation for the complex control of MSNA following acute hypoxia.     

Relationship between blood pressure,sleep K-complexes,and muscle sympathetic nerve activity in humans

Stage 2 sleep is characterized by the EEG appearance of "K-complexes" and blood pressure oscillations. K-complexes may be directly related to blood pressure changes or they may reflect central sympathetic activation. We analyzed the temporal relationship among K-complexes, heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) during sleep in eight healthy volunteers (3 men and 5 women, age 22-41 yr). Most K-complexes presented as single large complexes (56 +/- 20%), followed by single small complexes (15 +/- 14%) and as couplets or triplets (13 +/- 6%). Single large K-complexes were preceded by a baroreflex-mediated increase of MSNA in approximately one-half (55%) of the cases. Detailed analysis of HR, BP, and MSNA was possible in 63 (45%) large single K-complexes not disturbed by preceding baroreflex-related changes. Systolic and diastolic BP and MSNA increased significantly after single events (22.5 +/- 13, 5.2 +/- 2.1, and 6.5 +/- 3.0%). Mean sympathetic baroreflex latency was similar after the single large K-complexes compared with the mean value during stage 2 sleep (1,290 +/- 126 vs. 1,279 +/- 61 ms). The area under the burst was significantly increased after single large K-complexes (median 3.9 vs. 9.0 arbitrary units, P < 0.03). The results support the hypothesis that K-complexes express cortical activation leading to temporary facilitation of sympathetic outflow in a graded fashion. Their functional effects appear to be independent of baroreflex modulation of MSNA in approximately 50% of the cases.     

Autonomic and vascular responses to reduced limb perfusion.

The purpose of this study was to examine hemodynamic responses to graded muscle reflex engagement in human subjects. We studied seven healthy human volunteers [24 +/- 2 (SE) yr old; 4 men, 3 women] performing rhythmic handgrip exercise [40% maximal voluntary contraction (MVC)] during ambient and positive pressure exercise (+10 to +50 mmHg in 10-mmHg increments every minute). Muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), and mean blood velocity were recorded. Plasma lactate, hydrogen ion concentration, and oxyhemoglobin saturation were measured from venous blood. Ischemic exercise resulted in a greater rise in both MSNA and MAP vs. nonischemic exercise. These heightened autonomic responses were noted at +40 and +50 mmHg. Each level of positive pressure was associated with an immediate fall in flow velocity and forearm perfusion pressure. However, during each minute, perfusion pressure increased progressively. For positive pressure of +10 to +40 mmHg, this was associated with restoration of flow velocity. However, at +50 mmHg, flow was not restored. This inability to restore flow was seen at a time when the muscle reflex was clearly engaged (increased MSNA). We believe that these findings are consistent with the hypothesis that before the muscle reflex is clearly engaged, flow to muscle is enhanced by a process that raises perfusion pressure. Once the muscle reflex is clearly engaged and MSNA is augmented, flow to muscle is no longer restored by a similar rise in perfusion pressure, suggesting that active vasoconstriction within muscle is occurring at +50 mmHg.     

Fish oil and neurovascular control in humans

The antihypertensive influence of fish oil is controversial, and the mechanisms remain unclear. Because the inverse relation between fish oil and hypertension appears to be partially dependent on the degree of hypertension, we tested the hypothesis that fish oil would elicit more dramatic reductions in mean arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA) in prehypertensive (PHT) compared with normotensive (NT) subjects. Resting MAP, MSNA, and heart rate (HR) were examined before and after 8 wk of fish oil (9 g/day; 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid) or placebo (olive oil; 9 g/day) in 38 NT (19 fish oil; 19 placebo) and 29 PHT (15 fish oil; 14 placebo) volunteers. Fish oil did not alter resting MAP, MSNA, or HR in either NT (80 ± 1 to 80 ± 1 mmHg; 11 ± 2 to 10 ± 1 bursts/min; 71 ± 2 to 71 ± 2 beats/min) or PHT (88 ± 2 to 87 ± 1 mmHg; 11 ± 2 to 10 ± 2 bursts/min; 73 ± 2 to 73 ± 2 beats/min) subjects. When NT and PHT groups were consolidated, analysis of covariance confirmed that pretreatment resting MAP was not associated with changes in MSNA after fish oil. In contrast, pretreatment resting HR was correlated with changes in MSNA (r = 0.47; P = 0.007) and MAP (r = 0.42; P < 0.007) after fish oil but not placebo. In conclusion, fish oil did not alter sympathetic neural control in NT or PHT subjects. However, our findings suggest that fish oil is associated with modest sympathoinhibition in individuals with higher resting heart rates, a finding that is consistent with a recent meta-analysis examining the relations among fish oil, HR, and the risk of cardiovascular disease.     

Sex differences in carotid baroreflex control of arterial blood pressure in humans: relative contribution of cardiac output and total vascular conductance

It is presently unknown whether there are sex differences in the magnitude of blood pressure (BP) responses to baroreceptor perturbation or if the relative contribution of cardiac output (CO) and total vascular conductance (TVC) to baroreflex-mediated changes in BP differs in young women and men. Since sympathetic vasoconstrictor tone is attenuated in women, we hypothesized that carotid baroreflex-mediated BP responses would be attenuated in women by virtue of a blunted vascular response (i.e., an attenuated TVC response). BP, heart rate (HR), and stroke volume were continuously recorded during the application of 5-s pulses of neck pressure (NP; carotid hypotension) and neck suction (NS; carotid hypertension) ranging from +40 to -80 Torr in women (n = 20, 21 ± 0.5 yr) and men (n = 20, 21 ± 0.4 yr). CO and TVC were calculated on a beat-to-beat basis. Women demonstrated greater depressor responses to NS (e.g., -60 Torr, -17 ± 1%baseline in women vs. -11 ± 1%baseline in men, P < 0.05), which were driven by augmented decreases in HR that, in turn, contributed to larger reductions in CO (-60 Torr, -15 ± 2%baseline in women vs. -6 ± 2%baseline in men, P < 0.05). In contrast, pressor responses to NP were similar in women and men (e.g., +40 Torr, +14 ± 2%baseline in women vs. +10 ± 1%baseline in men, P > 0.05), with TVC being the primary mediating factor in both groups. Our findings indicate that sex differences in the baroreflex control of BP are evident during carotid hypertension but not carotid hypotension. Furthermore, in contrast to our hypothesis, young women exhibited greater BP responses to carotid hypertension by virtue of a greater cardiac responsiveness.     

Neurovascular responses to mental stress in prehypertensive humans

Neurovascular responses to mental stress have been linked to several cardiovascular diseases, including hypertension. Mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and forearm vascular responses to mental stress are well documented in normotensive (NT) subjects, but responses in prehypertensive (PHT) subjects remain unclear. We tested the hypothesis that PHT would elicit a more dramatic increase of MAP during mental stress via augmented MSNA and blunted forearm vascular conductance (FVC). We examined 17 PHT (systolic 120-139 and/or diastolic 80-89 mmHg; 22 ± 1 yr) and 18 NT (systolic < 120 and diastolic < 80 mmHg; 23 ± 2 yr) subjects. Heart rate, MAP, MSNA, FVC, and calf vascular conductance were measured during 5 min of baseline and 5 min of mental stress (mental arithmetic). Mental stress increased MAP and FVC in both groups, but the increases in MAP were augmented (Δ 10 ± 1 vs. Δ14 ± 1 mmHg; P < 0.05), and the increases in FVC were blunted (Δ95 ± 14 vs. Δ37 ± 8%; P < 0.001) in PHT subjects. Mental stress elicited similar increases in MSNA (Δ7 ± 2 vs. Δ6 ± 2 bursts/min), heart rate (Δ21 ± 3 vs. Δ18 ± 3 beats/min), and calf vascular conductance (Δ29 ± 10 vs. Δ19 ± 5%) in NT and PHT subjects, respectively. In conclusion, mental stress elicits an augmented pressor response in PHT subjects. This augmentation appears to be associated with altered forearm vascular, but not MSNA, responses to mental stress.     

Neural and cardiovascular responses to emotional stress in humans

Sympathetic neural responses to mental stress are well documented but controversial, whereas sympathetic neural responses to emotional stress are unknown. The purpose of this study was to investigate neural and cardiovascular responses to emotional stress evoked by negative pictures and reexamine the relationship between muscle sympathetic nerve activity (MSNA) and perceived stress. Mean arterial pressure (MAP), heart rate (HR), MSNA, and perceived stress levels were recorded in 18 men during three randomized trials: 1) neutral pictures, 2) negative pictures, and 3) mental stress. MAP and HR increased during mental stress (Delta14 +/- 2 mmHg and Delta15 +/- 2 beats/min, P < 0.001) but did not change during viewing of negative or neutral pictures. MSNA did not change during viewing of neutral (Delta1 +/- 1 burst/min, n = 16) or negative (Delta0 +/- 1 burst/min, n = 16) pictures or during mental stress (Delta1 +/- 2 burst/min, n = 13). Perceived stress levels were higher during mental stress (3 +/- 0 arbitrary units) than during viewing negative pictures (2 +/- 0 arbitrary units, P < 0.001). Perceived stress levels were not correlated to changes in MSNA during negative pictures (r = 0.10, P = 0.84) or mental stress (r = 0.36, P = 0.23). In conclusion, our results demonstrate robust increases in MAP and HR during mental stress, but not during emotional stress evoked by negative pictures. Although the influence of mental stress on MSNA remains unresolved, our findings challenge the concept that perceived stress levels modulate MSNA during mental stress.     

Low-dose estrogen therapy does not change postexercise hypotension, sympathetic nerve activity reduction, and vasodilation in healthy postmenopausal women

The aim of this study was to determine whether estrogen therapy enhances postexercise muscle sympathetic nerve activity (MSNA) decrease and vasodilation, resulting in a greater postexercise hypotension. Eighteen postmenopausal women received oral estrogen therapy (ET; n=9, 1 mg/day) or placebo (n=9) for 6 mo. They then participated in one 45-min exercise session (cycle ergometer at 50% of oxygen uptake peak) and one 45-min control session (seated rest) in random order. Blood pressure (BP, oscillometry), heart rate (HR), MSNA (microneurography), forearm blood flow (FBF, plethysmography), and forearm vascular resistance (FVR) were measured 60 min later. FVR was calculated. Data were analyzed using a two-way ANOVA. Although postexercise physiological responses were unaltered, HR was significantly lower in the ET group than in the placebo group (59+/-2 vs. 71+/-2 beats/min, P<0.01). In both groups, exercise produced significant decreases in systolic BP (145+/-3 vs. 154+/-3 mmHg, P=0.01), diastolic BP (71+/-3 vs. 75+/-2 mmHg, P=0.04), mean BP (89+/-2 vs. 93+/-2 mmHg, P=0.02), MSNA (29+/-2 vs. 35+/-1 bursts/min, P<0.01), and FVR (33+/-4 vs. 55+/-10 units, P=0.01), whereas it increased FBF (2.7+/-0.4 vs. 1.6+/-0.2 ml x min(-1) x 100 ml(-1), P=0.02) and did not change HR (64+/-2 vs. 65+/-2 beats/min, P=0.3). Although ET did not change postexercise BP, HR, MSNA, FBF, or FVR responses, it reduced absolute HR values at baseline and after exercise.     

Previous exercise attenuates muscle sympathetic activity and increases blood flow during acute euglycemic hyperinsulinemia.

Insulin infusion causes muscle vasodilation, despite the increase in sympathetic nerve activity. In contrast, a single bout of exercise decreases sympathetic activity and increases muscle blood flow during the postexercise period. We tested the hypothesis that muscle sympathetic activity would be lower and muscle vasodilation would be higher during hyperinsulinemia performed after a single bout of dynamic exercise. Twenty-one healthy young men randomly underwent two hyperinsulinemic euglycemic clamps performed after 45 min of seated rest (control) or bicycle exercise (50% of peak oxygen uptake). Muscle sympathetic nerve activity (MSNA, microneurography), forearm blood flow (FBF, plethysmography), blood pressure (BP, oscillometric method), and heart rate (HR, ECG) were measured at baseline (90 min after exercise or seated rest) and during hyperinsulinemic euglycemic clamps. Baseline glucose and insulin concentrations were similar in the exercise and control sessions. Insulin sensitivity was unchanged by previous exercise. During the clamp, insulin levels increased similarly in both sessions. As expected, insulin infusion increased MSNA, FBF, BP, and HR in both sessions (23 +/- 1 vs. 36 +/- 2 bursts/min, 1.8 +/- 0.1 vs. 2.2 +/- 0.2 ml.min(-1).100 ml(-1), 89 +/- 2 vs. 92 +/- 2 mmHg, and 58 +/- 1 vs. 62 +/- 1 beats/min, respectively, P < 0.05). BP and HR were similar between sessions. However, MSNA was significantly lower (27 +/- 2 vs. 31 +/- 2 bursts/min), and FBF was significantly higher (2.2 +/- 0.2 vs. 1.8 +/- 0.1 ml.min(-1).100 ml(-1), P < 0.05) in the exercise session compared with the control session. In conclusion, in healthy men, a prolonged bout of dynamic exercise decreases MSNA and increases FBF. These effects persist during acute hyperinsulinemia performed after exercise.     

Effects of naloxone on hemodynamics and sympathetic activity after exercise.

The effects of highdose naloxone (0.4 mg/kg iv) on hemodynamics and muscle sympathetic nerve activity (MSNA) after exercise were studied in nine normotensive young men randomly allocated the opioid antagonist or vehicle 30 min before treadmill exercise at 70% of resting heart rate reserve. Mean arterial pressure (MAP) was lower after exercise; cardiac output was increased. Mean values for MSNA and plasma norepinephrine were similar before and after exercise, but in individual subjects changes in resting MAP 60 min after exercise were inversely related to changes in sympathetic activity, suggesting that arterial baroreflex regulation of MSNA had been shifted to a lower set point. Naloxone did not prevent postexercise hypotension but transformed these inverse correlations into positive relationships. Naloxone attenuated both calf and systemic vasodilation without altering mean values for MSNA, indicating a peripheral effect of opioid antagonism. In normotensive subjects, naloxone alters the regulation of sympathetic outflow and vascular resistance during recovery from exercise but does not prevent the fall in MAP.     

Sex differences in forebrain and cardiovagal responses at the onset of isometric handgrip exercise: a retrospective fMRI study.

In general, cardiac regulation is dominated by the sympathetic and parasympathetic nervous systems in men and women, respectively. Our recent study had revealed sex differences in the forebrain network associated with sympathoexcitatory response to baroreceptor unloading. The present study further examined the sex differences in forebrain modulation of cardiovagal response at the onset of isometric exercise. Forebrain activity in healthy men (n = 8) and women (n = 9) was measured using functional magnetic resonance imaging during 5 and 35% maximal voluntary contraction handgrip exercise. Heart rate (HR), mean arterial pressure (MAP), and muscle sympathetic nerve activity (MSNA) were collected in a separate recording session. During the exercise, HR and MAP increased progressively, while MSNA was suppressed (P < 0.05). Relative to men, women demonstrated smaller HR (8 +/- 2 vs. 18 +/- 3 beats/min) and MAP (3 +/- 2 vs. 11 +/- 2 mmHg) responses to the 35% maximal voluntary contraction trials (P < 0.05). Although a similar forebrain network was activated in both groups, the smaller cardiovascular response in women was reflected in a weaker insular cortex activation. Nevertheless, men did not show a stronger deactivation at the ventral medial prefrontal cortex, which has been associated with modulating cardiovagal activity. In contrast, the smaller cardiovascular response in women related to their stronger suppression of the dorsal anterior cingulate cortex activity, which has been associated with sympathetic control of the heart. Our findings revealed sex differences in both the physiological and forebrain responses to isometric exercise.