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.     

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.     

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.     

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.     

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.     

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.     

Effects of short-term and prolonged bed rest on the vestibulosympathetic reflex

The mechanism(s) for post-bed rest (BR) orthostatic intolerance is equivocal. The vestibulosympathetic reflex contributes to postural blood pressure regulation. It was hypothesized that muscle sympathetic nerve responses to otolith stimulation would be attenuated by prolonged head-down BR. Arterial blood pressure, heart rate, muscle sympathetic nerve activity (MSNA), and peripheral vascular conductance were measured during head-down rotation (HDR; otolith organ stimulation) in the prone posture before and after short-duration (24 h; n = 22) and prolonged (36 ± 1 day; n = 8) BR. Head-up tilt at 80° was performed to assess orthostatic tolerance. After short-duration BR, MSNA responses to HDR were preserved (Δ5 ± 1 bursts/min, Δ53 ± 13% burst frequency, Δ65 ± 13% total activity; P < 0.001). After prolonged BR, MSNA responses to HDR were attenuated ～50%. MSNA increased by Δ8 ± 2 vs. Δ3 ± 2 bursts/min and Δ83 ± 12 vs. Δ34 ± 22% total activity during HDR before and after prolonged BR, respectively. Moreover, these results were observed in three subjects tested again after 75 ± 1 days of BR. This reduction in MSNA responses to otolith organ stimulation at 5 wk occurred with reductions in head-up tilt duration. These results indicate that prolonged BR (～5 wk) unlike short-term BR (24 h) attenuates the vestibulosympathetic reflex and possibly contributes to orthostatic intolerance following BR in humans. These results suggest a novel mechanism in the development of orthostatic intolerance in humans.     

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.     

Orthostatic hypotension in aging humans

We tested the hypothesis that hypotension occurred in older adults at the onset of orthostatic challenge as a result of vagal dysfunction. Responses of heart rate (HR) and mean arterial pressure (MAP) were compared between 10 healthy older and younger adults during onset and sustained lower body negative pressure (LBNP). A younger group was also assessed after blockade of the parasympathetic nervous system with the use of atropine or glycopyrrolate and after blockade of the beta(1)-adrenoceptor by use of metoprolol. Baseline HR (older vs. younger: 59 +/- 4 vs. 54 +/- 1 beats/min) and MAP (83 +/- 2 vs. 89 +/- 3 mmHg) were not significantly different between the groups. During -40 Torr, significant tachycardia occurred at the first HR response in the younger subjects without hypotension, whereas significant hypotension [change in MAP (DeltaMAP) -7 +/- 2 mmHg] was observed in the elderly without tachycardia. After the parasympathetic blockade, tachycardiac responses of younger subjects were diminished and associated with a significant hypotension at the onset of LBNP. However, MAP was not affected after the cardiac sympathetic blockade. We concluded that the elderly experienced orthostatic hypotension at the onset of orthostatic challenge because of a diminished HR response. However, an augmented vasoconstriction helped with the maintenance of their blood pressure during sustained LBNP.     

Regulation of muscle sympathetic nerve activity after bed rest deconditioning

Cardiovascular deconditioning reduces orthostatic tolerance. To determine whether changes in autonomic function might produce this effect, we developed stimulus-response curves relating limb vascular resistance, muscle sympathetic nerve activity (MSNA), and pulmonary capillary wedge pressure (PCWP) with seven subjects before and after 18 days of -6 degrees head-down bed rest. Both lower body negative pressure (LBNP; -15 and -30 mmHg) and rapid saline infusion (15 and 30 ml/kg body wt) were used to produce a wide variation in PCWP. Orthostatic tolerance was assessed with graded LBNP to presyncope. Bed rest reduced LBNP tolerance from 23.9 +/- 2.1 to 21.2 +/- 1.5 min, respectively (means +/- SE, P = 0.02). The MSNA-PCWP relationship was unchanged after bed rest, though at any stage of the LBNP protocol PCWP was lower, and MSNA was greater. Thus bed rest deconditioning produced hypovolemia, causing a shift in operating point on the stimulus-response curve. The relationship between limb vascular resistance and MSNA was not significantly altered after bed rest. We conclude that bed rest deconditioning does not alter reflex control of MSNA, but may produce orthostatic intolerance through a combination of hypovolemia and cardiac atrophy.     

Modulation of control of muscle sympathetic nerve activity during orthostatic stress in humans

We tested the hypothesis that orthostatic stress would modulate the arterial baroreflex (ABR)-mediated beat-by-beat control of muscle sympathetic nerve activity (MSNA) in humans. In 12 healthy subjects, ABR control of MSNA (burst incidence, burst strength, and total activity) was evaluated by analysis of the relation between beat-by-beat spontaneous variations in diastolic blood pressure (DAP) and MSNA during supine rest (CON) and at two levels of lower body negative pressure (LBNP: -15 and -35 mmHg). At -15 mmHg LBNP, the relation between burst incidence (bursts per 100 heartbeats) and DAP showed an upward shift from that observed during CON, but the further shift seen at -35 mmHg LBNP was only marginal. The relation between burst strength and DAP was shifted upward at -15 mmHg LBNP (vs. CON) and further shifted upward at -35 mmHg LBNP. At -15 mmHg LBNP, the relation between total activity and DAP was shifted upward from that obtained during CON and further shifted upward at -35 mmHg LBNP. These results suggest that ABR control of MSNA is modulated during orthostatic stress and that the modulation is different between a mild (nonhypotensive) and a moderate (hypotensive) level of orthostatic stress.     

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.     

Gender affects calf venous compliance at rest and during baroreceptor unloading in humans

Leg venous compliance is a determinant of peripheral venous pooling during orthostatic stress such that high venous compliance could contribute to reduced orthostatic tolerance. We tested the hypotheses that 1) calf venous compliance is reduced during baroreceptor unloading, and 2) calf venous compliance is greater in women than men. Twelve men (27 +/- 2 yr) and 12 women (25 +/- 2 yr) were studied in the supine posture. Calf venous compliance was determined by inflating a thigh venous collecting cuff to 60 mmHg for 8 min and then decreasing cuff pressure at a rate of 1 mmHg/s to 0 mmHg. The slope of the pressure-compliance relation (compliance = beta(1) + 2.beta(2).cuff pressure), which is the first derivative of the quadratic pressure-volume relation [(Deltalimb volume) = beta(0) + beta(1).(cuff pressure) + beta(2).(cuff pressure)(2)] during the reduction in collecting cuff pressure, was used to assess venous compliance at baseline and during one-legged lower body negative pressure (LBNP; -50 mmHg). At baseline, calf venous compliance was 48% lower (P < 0.001) in women than men and decreased in men (Delta-25 +/- 8%; P < 0.05) but not women (Delta1 +/- 11%) during LBNP. Rhythmic ischemic handgrip (Delta6 +/- 9%) and cold pressor testing (Delta-9 +/- 7%) did not alter calf venous compliance in a subgroup of men (n = 6). These data indicate gender-dependent effects on calf venous compliance under conditions associated with low sympathetic outflow (i.e., rest) and high sympathetic outflow (i.e., LBNP). However, they cannot explain gender-associated differences in orthostatic tolerance.     

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.     

Effects of lower body negative pressure on sympathetic discharge to leg muscles in humans

Recent studies indicate that nonhypotensive orthostatic stress in humans causes reflex vasoconstriction in the forearm but not in the calf. We used microelectrode recordings of muscle sympathetic nerve activity (MSNA) from the peroneal nerve in conscious humans to determine if unloading of cardiac baroreceptors during nonhypotensive lower body negative pressure (LBNP) increases sympathetic discharge to the leg muscles. LBNP from -5 to -15 mmHg had no effect on arterial pressure or heart rate but caused graded decreases in central venous pressure and corresponding large increases in peroneal MSNA. Total MSNA (burst frequency X mean burst amplitude) increased by 61 +/- 22% (P less than 0.05 vs. control) during LBNP at only -5 mmHg and rose progressively to a value that was 149 +/- 29% greater than control during LBNP at -15 mmHg (P less than 0.05). The major new conclusion is that nonhypotensive LBNP is a potent stimulus to muscle sympathetic outflow in the leg as well as the arm. During orthostatic stress in humans, the cardiac baroreflex appears to trigger a mass sympathetic discharge to the skeletal muscles in all of the extremities.     

Sympathetic vascular transduction is augmented in young normotensive blacks.

The purpose of the present study was to determine sympathetic vascular transduction in young normotensive black and white adults. We hypothesized that blacks would demonstrate augmented transduction of muscle sympathetic nerve activity (MSNA) into vascular resistance. To test this hypothesis, MSNA, forearm blood flow, heart rate, and arterial blood pressure were measured during lower body negative pressure (LBNP). At rest, no differences existed in arterial blood pressure, heart rate, forearm blood flow, and forearm vascular resistance (FVR). Likewise, LBNP elicited comparable responses of these variables for blacks and whites. Baseline MSNA did not differ between blacks and whites, but whites demonstrated greater increases during LBNP (28 +/- 7 vs. 55 +/- 18%, 81 +/- 21 vs. 137 +/- 42%, 174 +/- 81 vs. 556 +/- 98% for -5, -15, and -40 mmHg LBNP, respectively; P < 0.001). Consistent with smaller increases in MSNA but similar FVR responses during LBNP, blacks demonstrated greater sympathetic vascular transduction (%FVR/%MSNA) than whites (0.95 +/- 0.07 vs. 0.82 +/- 0.07 U; 0.82 +/- 0.11 vs. 0.64 +/- 0.09 U; 0.95 +/- 0.37 vs. 0.35 +/- 0.09 U; P < 0.01). In summary, young whites demonstrate greater increases in MSNA during baroreceptor unloading than age-matched normotensive blacks. However, more importantly, for a given increase in MSNA, blacks demonstrate greater forearm vasoconstriction than whites. This finding may contribute to augmented blood pressure reactivity in blacks.     

Effects of graded LBNP on MSNA and interstitial norepinephrine

Exposure to lower body negative pressure (LBNP) leads to an increased activation of the sympathetic nervous system (SNS) and an increase in muscle sympathetic nerve activity (MSNA). In this study, we examined the relationship between MSNA and interstitial norepinephrine (NE(i)) concentrations during LBNP. Twelve healthy volunteers were studied (26 +/- 6 yr). Simultaneous MSNA and microdialysis data were collected in six of these subjects. Measurements of MSNA (microneurography) and NE(i) (microdialysis, vastus lateralis) were performed at rest and then during an incremental LBNP paradigm (-10, -30, and -50 mmHg). MSNA rose as a function of LBNP (P < 0.001, n = 12). The plasma norepinephrine (NE(p)) concentration was 0.9 +/- 0.1 nmol/l at rest (n = 12). NE(i) measured in six subjects rose from 5.2 +/- 0.8 nmol/l at rest to 17.0 +/- 1.7 nmol/l at -50 mmHg (P < 0.001). Of note, the rise in NE(p) with LBNP was considerably less compared with the changes in NE(i) (Delta21 +/- 6% vs. Delta197 +/- 52%, n = 6, P < 0.015). MSNA and NE(i) showed a significant linear relationship (r = 0.721, P < 0.004). Activation of the SNS increased MSNA and NE(i) levels. The magnitude of the NE(i) increase was far greater than that seen for NE(p) suggesting that NE movement into the circulation decreases with baroreceptor unloading.     

Muscle sympathetic nerve activity during lower body negative pressure is accentuated in heat-stressed humans.

The purpose of this project was to test the hypothesis that increases in muscle sympathetic nerve activity (MSNA) during an orthostatic challenge is attenuated in heat-stressed individuals. To accomplish this objective, MSNA was measured during graded lower body negative pressure (LBNP) in nine subjects under normothermic and heat-stressed conditions. Progressive LBNP was applied at -3, -6, -9, -12, -15, -18, -21, and -40 mmHg for 2 min per stage. Whole body heating caused significant increases in sublingual temperature, skin blood flow, sweat rate, heart rate, and MSNA (all P < 0.05) but not in mean arterial blood pressure (P > 0.05). Progressive LBNP induced significant increases in MSNA in both thermal conditions. However, during the heat stress trial, increases in MSNA at LBNP levels higher than -9 mmHg were greater compared with during the same LBNP levels in normothermia (all P < 0.05). These data suggest that the increase in MSNA to orthostatic stress is not attenuated but rather accentuated in heat-stressed humans.     

Pathophysiology of orthostatic hypotension after bed rest: paradoxical sympathetic withdrawal

Although orthostatic hypotension is a common clinical syndrome after spaceflight and its ground-based simulation model, 6 degrees head-down bed rest (HDBR), the pathophysiology remains unclear. The authors' hypothesis that a decrease in sympathetic nerve activity is the major pathophysiology underlying orthostatic hypotension after HDBR was tested in a study involving 14-day HDBR in 22 healthy subjects who showed no orthostatic hypotension during 15-min 60 degrees head-up tilt test (HUT) at baseline. After HDBR, 10 of 22 subjects demonstrated orthostatic hypotension during 60 degrees HUT. In subjects with orthostatic hypotension, total activity of muscle sympathetic nerve activity (MSNA) increased less during the first minute of 60 degrees HUT after HDBR (314% of resting supine activity) than before HDBR (523% of resting supine activity, P < 0.05) despite HDBR-induced reduction in plasma volume (13% of plasma volume before HDBR). The postural increase in total MSNA continued during several more minutes of 60 degrees HUT while arterial pressure was maintained. Thereafter, however, total MSNA was paradoxically suppressed by 104% of the resting supine level at the last minute of HUT (P < 0.05 vs. earlier 60 degrees HUT periods). The suppression of total MSNA was accompanied by a 22 +/- 4-mmHg decrease in mean blood pressure (systolic blood pressure <80 mmHg). In contrast, orthostatic activation of total MSNA was preserved throughout 60 degrees HUT in subjects who did not develop orthostatic hypotension. These data support the hypothesis that a decrease in sympathetic nerve activity is the major pathophysiological factor underlying orthostatic hypotension after HDBR. It appears that the diminished sympathetic activity, in combination with other factors associated with HDBR (e.g., hypovolemia), may predispose some individuals to postural hypotension.