Forearm neurovascular responses during mental stress and vestibular activation

Autonomic responses may underlie associations among anxiety, vestibular dysfunction, and unexplained syncope. Mental stress (MS), an anxiety-inducing stimulus, causes forearm vasodilation, whereas the vestibulosympathetic reflex (VSR) causes forearm vasoconstriction. The purpose of this study was to examine the combined effects of mental and vestibular stimulation on neurovascular control in the forearm. Heart rate, arterial pressure (Finapres), and forearm blood flow (Doppler) were measured in 10 healthy volunteers in the prone position during 1) head-down rotation (HDR), 2) MS (mental arithmetic), and 3) HDR + MS. Forearm vascular resistance (FVR) increased during HDR (from 232 +/- 40 to 319 +/- 53 units) and decreased during MS (from 260 +/- 57 to 154 +/- 22 units). During HDR + MS, FVR did not change [change (Delta) = -31 +/- 50 units] and was not significantly different from the algebraic sum of each trial performed alone (Delta = -20 +/- 42 units). Arm muscle sympathetic nerve activity (MSNA; microneurography) was measured in seven additional subjects. MSNA increased during HDR (from 13 +/- 2 to 17 +/- 2 bursts/min) and HDR + MS (from 11 +/- 2 to 16 +/- 2 bursts/min). Increases in MSNA during HDR + MS (Delta = 5 +/- 2 bursts/min) were not different from the algebraic sum of each trial performed alone (Delta = 6 +/- 2 bursts/min). We conclude that an additive neurovascular interaction exists between MS and the VSR in the forearm. Activation of the VSR prevented forearm vasodilation during MS, suggesting that activation of the VSR may help protect against stress-induced syncope.     

Interactive effect of hypoxia and otolith organ engagement on cardiovascular regulation in humans.

We determined the interaction between the vestibulosympathetic reflex and the arterial chemoreflex in 12 healthy subjects. Subjects performed three trials in which continuous recordings of muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), heart rate (HR), and arterial oxygen saturation were obtained. First, in prone subjects the otolith organs were engaged by use of head-down rotation (HDR). Second, the arterial chemoreflex was activated by inspiration of hypoxic gas (10% O2 and 90% N2) for 7 min with HDR being performed during minute 6. Third, hypoxia was repeated (15 min) with HDR being performed during minute 14. HDR [means +/- SE; increase (Delta)7 +/- 1 bursts/min and Delta50 +/- 11% for burst frequency and total MSNA, respectively; P < 0.05] and hypoxia (Delta6 +/- 2 bursts/min and Delta62 +/- 29%; P < 0.05) increased MSNA. Additionally, MSNA increased when HDR was performed during hypoxia (Delta11 +/- 2 bursts/min and Delta127 +/- 57% change from normoxia; P < 0.05). These increases in MSNA were similar to the algebraic sum of the individual increase in MSNA elicited by HDR and hypoxia (Delta13 +/- 1 bursts/min and Delta115 +/- 36%). Increases in MAP (Delta3 +/- 1 mmHg) and HR (Delta19 +/- 1 beats/min) during combined HDR and hypoxia generally were smaller (P < 0.05) than the algebraic sum of the individual responses (Delta5 +/- 1 mmHg and Delta24 +/- 2 beats/min for MAP and HR, respectively; P < 0.05). These findings indicate an additive interaction between the vestibulosympathetic reflex and arterial chemoreflex for MSNA. Therefore, it appears that MSNA outputs between the vestibulosympathetic reflex and arterial chemoreflex are independent of one another in humans.     

Interaction of the vestibular system and baroreflexes on sympathetic nerve activity in humans

Muscle sympathetic nerve activity (MSNA) is altered by vestibular otolith stimulation. This study examined interactive effects of the vestibular system and baroreflexes on MSNA in humans. In study 1, MSNA was measured during 4 min of lower body negative pressure (LBNP) at either -10 or -30 mmHg with subjects in prone posture. During the 3rd min of LBNP, subjects lowered their head over the end of a table (head-down rotation, HDR) to engage the otolith organs. The head was returned to baseline upright position during the 4th min. LBNP increased MSNA above baseline during both trials with greater increases during the -30-mmHg trial. HDR increased MSNA further during the 3rd min of LBNP at -10 and -30 mmHg (Delta32% and Delta34%, respectively; P < 0.01). MSNA returned to pre-HDR levels during the 4th min of LBNP when the head was returned upright. In study 2, MSNA was measured during HDR, LBNP, and simultaneously performed HDR and LBNP. The sum of MSNA responses during individual HDR and LBNP trials was not significantly different from that observed during HDR and LBNP performed together (Delta131 +/- 28 vs. Delta118 +/- 47 units and Delta340 +/- 77 vs. Delta380 +/- 90 units for the -10 and -30 trials, respectively). These results demonstrate that vestibular otolith stimulation can increase MSNA during unloading of the cardiopulmonary and arterial baroreflexes. Also, the interaction between the vestibulosympathetic reflex and baroreflexes is additive in humans. These studies indicate that the vestibulosympathetic reflex may help defend against orthostatic challenges in humans by increasing sympathetic outflow.     

Vestibulosympathetic reflex during the early follicular and midluteal phases of the menstrual cycle

Evidence suggests that both the arterial baroreflex and vestibulosympathetic reflex contribute to blood pressure regulation, and both autonomic reflexes integrate centrally in the medulla cardiovascular center. A previous report indicated increased sympathetic baroreflex sensitivity during the midluteal (ML) phase of the menstrual cycle compared with the early follicular (EF) phase. On the basis of this finding, we hypothesize an augmented vestibulosympathetic reflex during the ML phase of the menstrual cycle. Muscle sympathetic nerve activity (MSNA), mean arterial pressure (MAP), and heart rate responses to head-down rotation (HDR) were measured in 10 healthy females during the EF and ML phases of the menstrual cycle. Plasma estradiol (Delta72 +/- 13 pg/ml, P < 0.01) and progesterone (Delta8 +/- 2 ng/ml, P < 0.01) were significantly greater during the ML phase compared with the EF phase. The menstrual cycle did not alter resting MSNA, MAP, and heart rate (EF: 13 +/- 3 bursts/min, 80 +/- 2 mmHg, 65 +/- 2 beats/min vs. ML: 14 +/- 3 bursts/min, 81 +/- 3 mmHg, 64 +/- 3 beats/min). During the EF phase, HDR increased MSNA (Delta3 +/- 1 bursts/min, P < 0.02) but did not change MAP or heart rate (Delta0 +/- 1 mmHg and Delta1 +/- 1 beats/min). During the ML phase, HDR increased both MSNA and MAP (Delta4 +/- 1 bursts/min and Delta3 +/- 1 mmHg, P < 0.04) with no change in heart rate (Delta0 +/- 1 beats/min). MSNA and heart rate responses to HDR were not different between the EF and ML phases, but MAP responses to HDR were augmented during the ML phase (P < 0.03). Our results demonstrate that the menstrual cycle does not influence the vestibulosympathetic reflex but appears to alter MAP responses to HDR during the ML phase.     

Effect of baroreflex loading on the responsiveness of the vestibulosympathetic reflex in humans.

Activation of the vestibular otolith organs with head-down rotation (HDR) increases muscle sympathetic nerve activity (MSNA) in humans. Previously, we demonstrated this vestibulosympathetic reflex (VSR) elicits increases in MSNA during baroreflex unloading (i.e., lower body negative pressure) in humans. Whether such an effect persists during baroreflex loading is unknown. We tested the hypothesis that the ability of the VSR to increase MSNA is preserved during baroreflex unloading and inhibited during baroreflex loading. Ten subjects (26 +/- 1 yr) performed three trials of HDR to activate the VSR. These trials were performed after a period of sustained saline (control), nitroprusside (baroreflex unloading: 0.8-1.0 microg.kg(-1).min(-1)), and phenylephrine (baroreflex loading: 0.6-0.8 microg.kg(-1).min(-1)) infusion. Nitroprusside infusion decreased (Delta7 +/- 1 mmHg, where Delta is change; P < 0.001) and phenylephrine infusion increased mean arterial pressure (Delta8 +/- 1 mmHg; P < 0.001) at rest. HDR performed during the control [Delta3 +/- 2 bursts/min, Delta314 +/- 154 arbitrary units (au) total activity, Delta41 +/- 18% total activity; P < 0.05] and nitroprusside trials [Delta5 +/- 2 bursts/min, Delta713 +/- 241 au total activity, Delta49 +/- 20% total activity; P < 0.05] increased MSNA similarly despite significantly elevated levels at rest (13 +/- 2 to 26 +/- 3 bursts/min) in the latter. In contrast, HDR performed during the phenylephrine trial failed to increase MSNA (Delta0 +/- 1 bursts/min, Delta-15 +/- 33 au total activity, Delta-8 +/- 21% total activity). These results confirm previous findings that the ability of the VSR to increase MSNA is preserved during baroreflex unloading. In contrast, the ability of the VSR to increase MSNA is abolished during baroreflex loading. These results provide further support for the concept that the VSR may act primarily to defend against hypotension in humans.     

Effect of thermal stress on the vestibulosympathetic reflexes in humans.

Both heat stress and vestibular activation alter autonomic responses; however, the interaction of these two sympathetic activators is unknown. To determine the effect of heat stress on the vestibulosympathetic reflex, eight subjects performed static head-down rotation (HDR) during normothermia and whole body heating. Muscle sympathetic nerve activity (MSNA; peroneal microneurography), mean arterial blood pressure (MAP), heart rate (HR), and internal temperature were measured during the experimental trials. HDR during normothermia caused a significant increase in MSNA (Delta5 +/- 1 bursts/min; Delta53 +/- 14 arbitrary units/min), whereas no change was observed in MAP, HR, or internal temperature. Whole body heating significantly increased internal temperature (Delta0.9 +/- 0.1 degrees C), MSNA (Delta10 +/- 3 bursts/min; Delta152 +/- 44 arbitrary units/min), and HR (Delta25 +/- 6 beats/min), but it did not alter MAP. HDR during whole body heating increased MSNA (Delta16 +/- 4 bursts/min; Delta233 +/- 90 arbitrary units/min from normothermic baseline), which was not significantly different from the algebraic sum of HDR during normothermia and whole body heating (Delta15 +/- 4 bursts/min; Delta205 +/- 55 arbitrary units/min). These data suggest that heat stress does not modify the vestibulosympathetic reflex and that both the vestibulosympathetic and thermal reflexes are robust, independent sympathetic nervous system activators.     

Greater sensitivity of the vestibulosympathetic reflex in the upright posture in humans.

Otolith organs have been shown to activate the sympathetic nervous system in the prone position by head-down rotation (HDR) in humans. To date, otolithic stimulation by HDR has not been comprehensively studied in the upright posture. The purpose of the present study was to determine whether otolithic stimulation increases muscle sympathetic nerve activity (MSNA) in the upright posture. It was hypothesized that stimulation of the otolith organs would increase MSNA in the upright posture, despite increased baseline sympathetic activation due to unloading of the baroreceptors. MSNA, arterial blood pressure, heart rate, and degree of head rotation were measured during HDR in 18 volunteers (23 +/- 1 yr) in different postures. Study 1 (n = 11) examined HDR in the prone and sitting positions and study 2 (n = 7) examined HDR in the prone and 60 degrees head-up tilt positions. Baseline MSNA was 8 +/- 4, 15 +/- 4, and 33 +/- 2 bursts/min for prone, sitting, and head-up tilt, respectively. HDR significantly increased MSNA in the prone (Delta4 +/- 1 and Delta105 +/- 37% for burst frequency and total activity, respectively), sitting (Delta5 +/- 1 and Delta43 +/- 12%), and head-up tilt (Delta7 +/- 1 and Delta110 +/- 41%; P < 0.05). Sensitivity of the vestibulosympathetic reflex (%DeltaMSNA/DeltaHDR; degree of head rotation) was significantly greater in the sitting and head-up tilt than prone position (prone = 74 +/- 22; sitting = 109 +/- 30; head-up tilt = 276 +/- 103; P < 0.05). These data indicate that stimulation of the otolith organs can mediate increases in MSNA in the upright posture and suggest a greater sensitivity of the vestibulosympathetic reflex in the upright posture in humans.     

Aging, opioid-receptor agonists and antagonists, and the vestibulosympathetic reflex in humans.

Animal studies indicate that opioids inhibit the firing rate of vestibular neurons, which are important in mediating the vestibulosympathetic reflex. Furthermore, this inhibition appears to be greater in more mature rats. In the present study, we tested the hypotheses that opioids inhibit the vestibulosympathetic reflex in humans and that endogenous opioids contribute to the age-related impairment of the vestibulosympathetic reflex. These hypotheses were tested by measuring muscle sympathetic nerve activity (MSNA), arterial blood pressure, and heart rate responses to otolith organ engagement during head-down rotation (HDR) in young (24 +/- 2 yr old) and older (63 +/- 2 yr) subjects before and after administration of either an opioid-receptor antagonist (16 mg naloxone in 9 young and 8 older subjects) or an opioid-receptor agonist (60 mg codeine in 7 young and 7 older subjects). Naloxone did not augment the reflex increase in MSNA during HDR in young (Delta7 +/- 2 vs. Delta4 +/- 2 bursts/min and Delta81 +/- 23 vs. Delta60 +/- 24% change in burst frequency and total MSNA before and after naloxone, respectively) or older subjects (Delta2 +/- 2 vs. Delta1 +/- 2 burst/min and Delta8 +/- 7 vs. Delta8 +/- 9% before and after naloxone). Similarly, codeine did not attenuate the increase in MSNA during HDR in young (Delta8 +/- 1 vs. Delta7 +/- 2 bursts/min and Delta53 +/- 4 vs. Delta64 +/- 16% before and after codeine) or older subjects (Delta6 +/- 4 vs. Delta3 +/- 3 bursts/min and Delta38 +/- 21 vs. Delta33 +/- 20%). Mean arterial blood pressure and heart rate responses to HDR were not altered by either naloxone or codeine. These data do not provide experimental support for the concept that opioids modulate the vestibulosympathetic reflex in humans. Moreover, endogenous opioids do not appear to contribute the age-associated impairment of the vestibulosympathetic reflex.     

Relationship between muscle sympathetic nerve activity and systemic hemodynamics during nitric oxide synthase inhibition in humans

Large interindividual differences exist in resting sympathetic nerve activity (SNA) among normotensive humans with similar arterial pressure (AP). We recently showed inverse relationships of resting SNA with cardiac output (CO) and vascular adrenergic responsiveness that appear to balance the influence of differences in SNA on blood pressure. In the present study, we tested whether nitric oxide (NO)-mediated vasodilation has a role in this balance by evaluating hemodynamic responses to systemic NO synthase (NOS) inhibition in individuals with low and high resting muscle SNA (MSNA). We measured MSNA via peroneal microneurography, CO via acetylene uptake and AP directly, at baseline and during increasing systemic doses of the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA). Baseline MSNA ranged from 9 to 38 bursts/min (13 to 68 bursts/100 heartbeats). L-NMMA caused dose-dependent increases in AP and total peripheral resistance and reflex decreases in CO and MSNA. Increases in AP with L-NMMA were greater in individuals with high baseline MSNA (PANOVA<0.05). For example, after 8.5 mg/kg of L-NMMA, in the low MSNA subgroup (n=6, 28+/-4 bursts/100 heartbeats), AP increased 9+/-1 mmHg, whereas in the high-MSNA subgroup (n=6, 58+/-3 bursts/100 heartbeats), AP increased 15+/-2 mmHg (P<0.01). The high-MSNA subgroup had lower baseline CO and smaller decreases in CO with L-NMMA, but changes in total peripheral resistance were not different between groups. We conclude that differences in CO among individuals with varying sympathetic traffic have important hemodynamic implications during disruption of NO-mediated vasodilation.     

Neurovascular responses to mental stress in the supine and upright postures.

The purpose of this study was to determine neurovascular responses to mental stress (MS) in the supine and upright postures. MS was elicited in 23 subjects (26 +/- 1 yr) by 5 min of mental arithmetic. In study 1 (n = 9), Doppler ultrasound was used to measure mean blood flow velocity in the renal (RBFV) and superior mesenteric arteries (SMBFV), and venous occlusion plethysmography was used to measure forearm blood flow (FBF). In study 2 (n = 14), leg blood flow (LBF; n = 9) was measured by Doppler ultrasound, and muscle sympathetic nerve activity (MSNA; n = 5) was measured by microneurography. At rest, upright posture increased heart rate and MSNA and decreased LBF, FBF, RBFV, and SMBFV and their respective conductances. MS elicited similar increases in mean arterial blood pressure ( approximately 12 mmHg) and heart rate ( approximately 17 beats/min), regardless of posture. MS in both postures elicited a decrease in RBFV, SMBFV, and their conductances and an increase in LBF, FBF, and their conductances. Changes in blood flow were blunted in the upright posture in all vascular beds examined, but the pattern of the vascular response was the same as the supine posture. MS did not change MSNA in either posture (change: approximately 1 +/- 3 and approximately 3 +/- 3 bursts/min, respectively). In conclusion, the augmented sympathetic activity of the upright posture does not alter heart rate, mean arterial blood pressure, or MSNA responses to MS. MS elicits divergent vascular responses in the visceral and peripheral vasculature. These results indicate that, although the upright posture attenuates vascular responses to MS, the pattern of neurovascular responses does not differ between postures.     

Vestibulosympathetic reflex during orthostatic challenge in aging humans

Aging attenuates the increase in muscle sympathetic nerve activity (MSNA) and elicits hypotension during otolith organ engagement in humans. The purpose of the present study was to determine the neural and cardiovascular responses to otolithic engagement during orthostatic stress in older adults. We hypothesized that age-related impairments in the vestibulosympathetic reflex would persist during orthostatic challenge in older subjects and might compromise arterial blood pressure regulation. MSNA, arterial blood pressure, and heart rate responses to head-down rotation (HDR) performed with and without lower body negative pressure (LBNP) in prone subjects were measured. Ten young (27 +/- 1 yr) and 11 older subjects (64 +/- 1 yr) were studied prospectively. HDR performed alone elicited an attenuated increase in MSNA in older subjects (Delta106 +/- 28 vs. Delta20 +/- 7% for young and older subjects). HDR performed during simultaneous orthostatic stress increased total MSNA further in young (Delta53 +/- 15%; P < 0.05) but not older subjects (Delta-5 +/- 4%). Older subjects demonstrated consistent significant hypotension during HDR performed both alone (Delta-6 +/- 2 mmHg) and during LBNP (Delta-7 +/- 2 mmHg). These data provide experimental support for the concept that age-related impairments in the vestibulosympathetic reflex persist during orthostatic challenge in older adults. Furthermore, these findings are consistent with the concept that age-related alterations in vestibular function might contribute to altered orthostatic blood pressure regulation with age in humans.     

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.     

Human cerebrovascular and autonomic rhythms during vestibular activation

Otolith activation increases muscle sympathetic nerve activity (MSNA), and MSNA activation may alter associations among autonomic oscillators, including those modulating cerebral hemodynamics. The purpose of this study was to determine the influence of vestibulosympathetic activation on cerebral and autonomic rhythms. We recorded the ECG, finger arterial pressure, end-tidal CO(2), respiration, cerebral blood flow velocity, and MSNA in eight subjects. Subjects breathed at 0.25 Hz for 5 min in the prone and head-down positions. We analyzed data in time and frequency domains and performed cross-spectral analyses to determine coherence and transfer function magnitude. Head-down rotation increased MSNA from 7 +/- 1.3 to 12 +/- 1.5 bursts/min (P = 0.001) but did not affect R-R intervals, arterial pressures, mean cerebral blood flow velocities (V(mean)), or their power spectra. Vestibular activation with head-down rotation had no effect on mean arterial pressure and V(mean) transfer function magnitude. The two new findings from this study are 1) head-down rotation independently activates the sympathetic nervous system with no effect on parasympathetic activity or V(mean); and 2) frequency-dependent associations between arterial pressures and V(mean) are independent of vestibular activation. These findings support the concept that vestibular-autonomic interactions independently and redundantly serve to maintain steady-state hemodynamics.     

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.     

Effects of lower body positive pressure on muscle sympathetic nerve activity response to head-up tilt

The present study was performed to test the hypothesis that application of lower body positive pressure (LBPP) during orthostasis would reduce the baroreflex-mediated enhancement in sympathetic activity in humans. Eight healthy young men were exposed to a 70 degrees head-up tilt (HUT) on application of 30 mmHg LBPP. Muscle sympathetic nerve activity (MSNA) was microneurographically recorded from the tibial nerve, along with hemodynamic variables. We found that in the supine position with LBPP, MSNA remained unchanged (13.4 +/- 3.3 vs. 11.8 +/- 2.3 bursts/min, without vs. with LBPP; P > 0.05), mean arterial pressure was elevated, but arterial pulse pressure and heart rate did not alter. At 70 degrees HUT with LBPP, the enhanced MSNA response was reduced (33.8 +/- 5.0 vs. 22.5 +/- 2.2 bursts/min, without vs. with LBPP; P < 0.05), mean arterial pressure was higher, the decreased pulse pressure was restored, and the increased heart rate was attenuated. We conclude that the baroreflex-mediated enhancement in sympathetic activity during HUT was reduced by LBPP. Application of LBPP in HUT induced an obvious cephalad fluid shift as well as a restoration of arterial pulse pressure, which reduced the inhibition of the baroreceptors. However, the activation of the intramuscular mechanoreflexes produced by 30 mmHg LBPP might counteract the effects of baroreflexes.     

Isometric handgrip training reduces arterial pressure at rest without changes in sympathetic nerve activity

The purpose of this study was to determine whether isometric handgrip (IHG) training reduces arterial pressure and whether reductions in muscle sympathetic nerve activity (MSNA) mediate this drop in arterial pressure. Normotensive subjects were assigned to training (n = 9), sham training (n = 7), or control (n = 8) groups. The training protocol consisted of four 3-min bouts of IHG exercise at 30% of maximal voluntary contraction (MVC) separated by 5-min rest periods. Training was performed four times per week for 5 wk. Subjects' resting arterial pressure and heart rate were measured three times on 3 consecutive days before and after training, with resting MSNA (peroneal nerve) recorded on the third day. Additionally, subjects performed IHG exercise at 30% of MVC to fatigue followed by muscle ischemia. In the trained group, resting diastolic (67 +/- 1 to 62 +/- 1 mmHg) and mean arterial pressure (86 +/- 1 to 82 +/- 1 mmHg) significantly decreased, whereas systolic arterial pressure (116 +/- 3 to 113 +/- 2 mmHg), heart rate (67 +/- 4 to 66 +/- 4 beats/min), and MSNA (14 +/- 2 to 15 +/- 2 bursts/min) did not significantly change following training. MSNA and cardiovascular responses to exercise and postexercise muscle ischemia were unchanged by training. There were no significant changes in any variables for the sham training and control groups. The results indicate that IHG training is an effective nonpharmacological intervention in lowering arterial pressure.     

Effect of gender on vestibular sympathoexcitation

Studies have suggested that premenopausal women are more prone to orthostatic intolerance than men. Additionally, it has been postulated that the vestibulosympathetic reflex is important in regulating postural-related changes in sympathetic activity. The purpose of the present study was to determine whether men and women differ in their sympathetic and cardiovascular responses to stimulation of the otolith organs elicited by head-down rotation (HDR). Heart rate (HR), arterial pressure, calf blood flow (CBF), and leg muscle sympathetic nerve activity (MSNA) were measured during 3 min of HDR in the prone posture in 33 women and 30 men. With the exception of HR (71 +/- 2 and 63 +/- 1 beats/min for women and men, respectively; P < 0.01), all baseline variables were not different between genders. There were no gender differences in responses to HDR. MSNA increased 72 +/- 33 units (43%) in the men and 88 +/- 15 units (59%) in the women during HDR (P < 0.01). CBF decreased [-0.6 +/- 0.1 (15%) and -0.5 +/- 0.1 (19%) ml. min(-1). 100 ml(-1)] and calf vascular resistance increased [8 +/- 2 (21%) and 11 +/- 3 (25%) units during HDR for men and women, respectively (P < 0.01)]. Both in the men and women, HR increased 2 +/- 1 beats/min (P < 0.01). These results demonstrate that sympathetic activation during HDR in the prone posture is similar in men and women. Therefore, these findings suggest that the vestibulosympathetic reflex is not different between healthy men and women.     

Glycerol-induced fluid shifts attenuate the vestibulosympathetic reflex in humans

The glycerol dehydration test (GDT) has been used to test for the presence of Ménière's disease and elicits acute alterations in vestibular reflexes in both normal and pathological states. Activation of the vestibulosympathetic reflex (VSR) increases muscle sympathetic nerve activity (MSNA) and peripheral vascular resistance. We hypothesized that the GDT would attenuate the VSR through fluid shifts of the inner ear. Sixteen male subjects (26 ± 1 yr) were randomly assigned to be administered either glycerol mixed with cranberry juice (97 ± 3 ml glycerol + equal portion of cranberry juice; n = 9) or a placebo control [water + cranberry juice (100 ml each); n = 7]. Subjects in both groups performed head-down rotation (HDR), which engages the VSR, before and after administration of either the glycerol or placebo. MSNA (microneurography), arterial blood pressure, and leg blood flow (venous occlusion plethysmography) were measured during HDR. Before glycerol administration, HDR significantly increased MSNA burst frequency (Δ8 ± 1 bursts/min; P < 0.01) and total activity (Δ77 ± 18%; P < 0.01) and decreased calf vascular conductance (-Δ20 ± 3%; P < 0.01). However, HDR performed postadministration of glycerol resulted in an attenuated MSNA increase (Δ3 ± 1 bursts/min, Δ22 ± 3% total activity) and decrease in calf vascular conductance (-Δ7 ± 4%). HDR significantly increased MSNA burst frequency (Δ5 ± 1 and Δ5 ± 2 bursts/min) and total activity (Δ58 ± 13% and Δ52 ± 18%) in the placebo group before and after placebo, respectively (P < 0.01). Likewise, decreases in calf vascular conductance during HDR before and after placebo were not different (-Δ13 ± 4% and -Δ14 ± 2%, respectively; P < 0.01). These results suggest that fluid shifts of the inner ear via glycerol dehydration attenuate the VSR. These data provide support that inner ear fluid dynamics can have a significant impact on blood pressure regulation via the VSR in humans.     

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.     

Central chemoreflex sensitivity and sympathetic neural outflow in elite breath-hold divers.

Repeated hypoxemia in obstructive sleep apnea patients increases sympathetic activity, thereby promoting arterial hypertension. Elite breath-holding divers are exposed to similar apneic episodes and hypoxemia. We hypothesized that trained divers would have increased resting sympathetic activity and blood pressure, as well as an excessive sympathetic nervous system response to hypercapnia. We recruited 11 experienced divers and 9 control subjects. During the diving season preceding the study, divers participated in 7.3 +/- 1.2 diving fish-catching competitions and 76.4 +/- 14.6 apnea training sessions with the last apnea 3-5 days before testing. We monitored beat-by-beat blood pressure, heart rate, femoral artery blood flow, respiration, end-tidal CO(2), and muscle sympathetic nerve activity (MSNA). After a baseline period, subjects began to rebreathe a hyperoxic gas mixture to raise end-tidal CO(2) to 60 Torr. Baseline MSNA frequency was 31 +/- 11 bursts/min in divers and 33 +/- 13 bursts/min in control subjects. Total MSNA activity was 1.8 +/- 1.5 AU/min in divers and 1.8 +/- 1.3 AU/min in control subjects. Arterial oxygen saturation did not change during rebreathing, whereas end-tidal CO(2) increased continuously. The slope of the hypercapnic ventilatory and MSNA response was similar in both groups. We conclude that repeated bouts of hypoxemia in elite, healthy breath-holding divers do not lead to sustained sympathetic activation or arterial hypertension. Repeated episodes of hypoxemia may not be sufficient to drive an increase in resting sympathetic activity in the absence of additional comorbidities.