Vestibulosympathetic Reflex Research Articles

The change in Baroreflex Regulation of Heart Rhythm after “Dry” Immersion Appears during Orthostasis, but not Lower Body Negative Pressure Test

The ratio of low-frequency (LF, ~0.1 Hz) waves of RR interval duration (RRI) and systolic blood pressure (SAP) reflects the cardiac baroreflex sensitivity (BRS). Gravitational unloading (GU) may alter BRS during the passive orthostatic test (HUT) and lower body negative pressure (LBNP) test. Both effects cause blood redistribution to the lower body, but HUT is accompanied by greater unloading of sinocarotid baroreceptors than LBNP and activation of the vestibulosympathetic reflex but GU effects on BRS in these tests have not been directly compared previously. In this study we tested the hypothesis that the effect of “dry” immersion (DI, on-ground model of GU) on BRS in the same subjects will be more pronounced during HUT than during LBNP, which causes a comparable decrease in stroke volume. Nine healthy men participated in two test sessions (before and after 7-day DI) consisting of five 3-min HUT (65°) and five 3-min LBNP (–35 mmHg) with averaging the parameters in each test. Wavelet analysis was used to determine the amplitude of the RRI and SAP waves in the range of 0.05–0.13 Hz. The amplitude of LF waves of SAP increased in both tests, after DI - more significantly in HUT. The amplitude of LF RRI waves decreased in the two tests; the degree of decrease did not differ between tests and did not change under the influence of DI. The α-coefficient (the ratio of the amplitudes of RRI and SAP LF waves) decreased equally in the two tests before DI, but after DI, the degree of α-coefficient reduction increased in HUT test but did not change in LBNP test. Thus, the effect of DI on BRS is evident in HUT, but not in LBNP, which may be explained by the more pronounced influence of HUT on the mechanisms of neural control of heart rhythm.

Effect of the early diastolic blood pressure response to the head-up tilt test on the recurrence of benign paroxysmal positional vertigo.

Otolith organ acts complementarily with the autonomic nervous system to maintain blood pressure. However, the effect of blood pressure variability in the autonomic nervous system on otolith organ has not yet been determined. This study aimed to verify the hypothesis that blood pressure variability in the autonomic nervous system affects the recurrence of benign paroxysmal positional vertigo (BPPV), which is the most common disease of the vestibular organs, by using the head-up tilt test (HUTT). This study included 432 patients diagnosed with idiopathic BPPV. The follow-up period for all patients was 12 months. Age, sex, hypertension, diabetes and recurrence were analyzed. The HUTT parameters were divided into a group of patients whose average diastolic blood pressure increased in the upright position compared to supine position during the HUTT (DBP1) and a group of patients whose average diastolic blood pressure decreased in the upright position compared to supine position during the HUTT (DBP2). Model selection, general loglinear analysis, and logit loglinear analysis were performed using a hierarchically progressing loglinear analysis. In summary, the group with increased average diastolic blood pressure (DBP1) showed a higher tendency for BPPV recurrence compared to the group with decreased diastolic blood pressure (DBP2) in the upright position during the HUTT, although the difference was not statistically significant (p = 0.080). However, in males, the DBP1 group demonstrated a significantly higher recurrence rate of BPPV than the DBP2 group during the HUTT (95% CI, -20.021 to -16.200; p < 0.001). It is presumed that poor autonomic nervous system response through vestibulosympathetic reflex maintains elevated diastolic blood pressure in the upright position during the HUTT. This variability is assumed to affect the recurrence of BPPV.

A study of otolith function in patients with orthostatic dizziness.

Orthostatic dizziness (OD) is the dizziness that occurs when moving from a sitting or a supine to a standing position. It is typically thought to be connected to orthostatic hypotension (OH). The otolithic control of respiratory and cardiovascular system through vestibulosympathetic reflex has been the focus of considerable recent interest. This study aimed to evaluate the relationship between the orthostatic dizziness and otolith organ function. This study was carried on 50 adults aged from 18 to 50years with normal peripheral hearing. Subjects were divided into two groups: controls (GI): 20 healthy adults and study group (GII): 30 patients who were complaining of OD. Patients were submitted to; blood pressure measurement in sitting and standing positions, combined vestibular-evoked myogenic potentials (VEMPs) and subjective visual vertical and horizontal tests (SVV) and (SVH). The study group showed abnormal absent cVEMP, oVEMP. There were also statistically significant differences of P13 and N23 latencies and (P13N23) amplitudes between the two groups in the left ears. Both groups differed significantly in SVH values deviated to the left side. Study group were further subdivided into ten patients with OH and 20 patients with OD without OH. The both study subgroups showed abnormal absent cVEMP, oVEMP and abnormal SVH. OH patients showed statistically significant differences of cVEMP waves P13, N23 latencies in the left ears when compared with the control. Otolith malfunction may be the cause of orthostatic dizziness (OD) in patients with and without orthostatic hypotension.

Vestibular syncope: clinical characteristics and mechanism.

Background and ObjectivesVestibular syncope is a condition in which vertigo‐induced hemodynamic changes cause syncope. This study investigated the clinical and laboratory findings of vestibular syncope and tried to refine our knowledge of the mechanism underlying this newly recognized entity.MethodsThis study retrospectively analyzed 53 patients (33 women, median age = 63 years [interquartile range = 54–71 years]) with vestibular syncope from January 2017 to December 2021. To explain the mechanism of vestibular syncope, we incorporated a velocity‐storage model into the dual reflex pathways comprising the vestibulo‐sympathetic reflex and baroreflex and predicted the cardiovascular responses.ResultsTwenty (37.7%) patients had multiple episodes of vestibular syncope, and seven (13.2%) had potentially life‐threatening injuries. Meniere's disease (20.8%) and benign paroxysmal positional vertigo (9.4%) were the most common underlying vestibular disorders. Abnormal vestibular function tests included impaired cervical vestibular‐evoked myogenic potentials (57.5%) and positive head impulse tests (31.0%). Orthostatic hypotension was found in 19.5% of patients. Dyslipidemia (30.2%) and hypertension (28.3%) were common medical comorbidities. The dual reflex pathways incorporating the function of the velocity‐storage circuit in the brainstem and cerebellum suggest that vestibular syncope is a neurally mediated reflex syncope associated with a sudden hemodynamic change during vertigo. This change can be arterial hypertension triggered by a false downward inertial cue, as suggested previously, or hypotension driven by a false upward inertial cue.ConclusionsVestibular syncope is associated with various vestibular disorders and requires careful evaluation and intervention to prevent recurrent falls and significant injuries.

Relationship between orthostatic hypotension and recurrence of benign paroxysmal positional vertigo

Blood pressure is maintained by a combined mechanism of the baroreceptor reflex and the vestibulosympathetic reflex. This study is intended to verify the hypothesis that the orthostatic hypotension (OH) seen when benign paroxysmal positional vertigo (BPPV) occurred may act as a factor that affects the recurrence of BPPV. The subjects of present study were selected from among 239 patients diagnosed with idiopathic BPPV. The average age of the group with OH was 59.3 years, and the age of the group without OH was 50.3 years, with a statistically significant difference (P = 0.013). It was shown that drug-taking increased the risk of OH occurrence by 4.08 times (C.I for exp(B): 1.20–13.77) compared to the group that did not take drugs. It was shown that the risk of recurrence of BPPV was significantly reduced in the no recurrence group compared to the multiple recurrence group when there was no OH (p = 0.000; aOR 0.0000002). Also, the risk of recurrence was significantly reduced in the no recurrence group compared to the multiple recurrence group when there was no drug-taking (p = 0.000 aOR 0.0000001). This study is the first study that studied the effect of OH on the recurrence of BPPV and showed the possibility that OH could partially influence the recurrence of BPPV.

Vestibular-autonomic interactions: beyond orthostatic dizziness.

This review aims to summarize the current literature describing vestibular-autonomic interactions and to describe their putative role in various disorders' clinical presentations, including orthostatic dizziness and motion sensitivity. The vestibular-autonomic reflexes have long been described as they relate to cardiovascular and respiratory function. Although orthostatic dizziness may be in part related to impaired vestibulo-sympathetic reflex (orthostatic hypotension), there are various conditions that may present similarly. A recent clinical classification aims to improve identification of individuals with hemodynamic orthostatic dizziness so that appropriate recommendations and management can be efficiently addressed. Researchers continue to improve understanding of the underlying vestibular-autonomic reflexes with recent studies noting the insular cortex as a cortical site for vestibular sensation and autonomic integration and modulation. Work has further expanded our understanding of the clinical presentation of abnormal vestibular-autonomic interactions that may occur in various conditions, such as aging, peripheral vestibular hypofunction, traumatic brain injury, and motion sensitivity. The vestibular-autonomic reflexes affect various sympathetic and parasympathetic functions. Understanding these relationships will provide improved identification of underlying etiology and drive improved patient management.

Abstract P204: Sinusoidal Galvanic Stimulation Improves Orthostatic Symptoms In Patients With Postural Tachycardia.

Postural Tachycardia Syndrome (POTS) is characterized by frequent orthostatic symptoms and excessive heart rate increase (&gt;= 30 bpm) on standing in the absence of orthostatic hypotension for more than 6 months. We and others have described a vestibulo-sympathetic reflex that can be engaged by galvanic vestibular stimulation to modulate sympathetic activity (Biaggioni et al., 2000; Kaufmann et al., 2002; Monahan &amp; Ray, 2002; Ray &amp; Carter, 2003, Bent, Macefield et al. 2006). We hypothesize that habituation to sinusoidal galvanic vestibular stimulation will improve orthostatic tolerance. We studied 6 patients with POTS (30.5+/6.0 years, BMI 22.8+/-2.9 kg/m 2 ) in two sessions using sinusoidal galvanic vestibular stimulation (sGVS 0.025 Hz, 2mA) or sham (0.01 mA). Stimulation was applied near mastoid process for 30 min in semi-recumbent position before orthostatic challenge. Patient were upright for a maximum of 15 minutes after each stimulation. Orthostatic change in Vanderbilt Orthostatic Symptom Score (dVOSS), orthostatic heart rate increase (dHR) and blood pressure response were recorded. Non-parametric Wilcoxon test for paired measures with significance level p&lt;0.05 was used. sGVS stimulation reduced overall orthostatic symptom score (dVOSS sham: 32.5+/-9.3 bpm vs dVOSS sGVS: 10.5+/-5.5, p=0.03) and tended to reduce orthostatic HR increase (dHR sham: 65.83+/-11.5 vs dHR sGVS: 46.5+/-10.7 bpm, p=0.06). Blood pressure and tilt time did not change. This pilot study suggests that habituation to sinusoidal vestibular could be used to improve orthostatic symptoms and orthostatic tolerance.

Responses of Neurons in the Medullary Lateral Tegmental Field and Nucleus Tractus Solitarius to Vestibular Stimuli in Conscious Felines.

Considerable evidence shows that the vestibular system contributes to adjusting sympathetic nervous system activity to maintain adequate blood pressure during movement and changes in posture. However, only a few prior experiments entailed recordings in conscious animals from brainstem neurons presumed to convey baroreceptor and vestibular inputs to neurons in the rostral ventrolateral medulla (RVLM) that provide inputs to sympathetic preganglionic neurons in the spinal cord. In this study, recordings were made in conscious felines from neurons in the medullary lateral tegmental field (LTF) and nucleus tractus solitarius (NTS) identified as regulating sympathetic nervous system activity by exhibiting changes in firing rate related to the cardiac cycle, or cardiac-related activity (CRA). Approximately 38% of LTF and NTS neurons responded to static 40° head up tilts with a change in firing rate (increase for 60% of the neurons, decrease for 40%) of ~50%. However, few of these neurons responded to 10° sinusoidal rotations in the pitch plane, in contrast to prior findings in decerebrate animals that the firing rates of both NTS and LTF neurons are modulated by small-amplitude body rotations. Thus, as previously demonstrated for RVLM neurons, in conscious animals NTS and LTF neurons only respond to large rotations that lead to changes in sympathetic nervous system activity. The similar responses to head-up rotations of LTF and NTS neurons with those documented for RVLM neurons suggest that LTF and NTS neurons are components of the vestibulo-sympathetic reflex pathway. However, a difference between NTS/LTF and RVLM neurons was variability in CRA over time. This variability was significantly greater for RVLM neurons, raising the hypothesis that the responsiveness of these neurons to baroreceptor input is adjusted based on the animal's vigilance and alertness.

The integrated functions of the cardiac autonomic and vestibular/oculomotor systems in adolescents following severe traumatic brain injury and typically developing controls

ABSTRACT Introduction The cardiac autonomic control system (CACS) is frequently impaired post-traumatic brain injury (TBI). However, the prevalence of vestibular/oculomotor impairment is less studied. These two systems interact during position change and contribute to blood-pressure regulation through the vestibulo-sympathetic reflex. Aim: To assess the CACS, the vestibular/oculomotor systems and their integrative function in adolescents post-TBI compared to typically-developing (TD) adolescents. Methods: 19 adolescents in the subacute stage following a severe TBI (14–117 days post injury) and 19 age and sex matched TD controls were recruited. Heart Rate Variability (HRV) was assessed at rest and during a modified tilt-test. A quantified version of the Vestibular/Ocular-Motor Screening (VOMS) was also administered. Results: At rest, the TBI group had higher HR and lower HRV values (p < .001). All participants with TBI demonstrated impairments in the VOMS (median of positive tests: 5 [range 2–9]) compared to only 6 out of 19 in the TD participants (median 0 [0–2]) (z = −5.34; p < .001). In response to the modified tilt test, the HRV increased significantly in the lifting period and decreased significantly once in standing only in the TBI group (z = −2.85, p = .025). Conclusion: Adolescents post severe TBI demonstrated impairments in the CACS, positive tests on the VOMS and significantly greater changes in the modified tilt test as compared to TD. Clinical trial gov. number: NCT03215082

Vestibular and Cardiovascular Responses After Long-Duration Spaceflight.

BACKGROUND: The vestibulo-sympathetic reflex operates during orthostatically challenging movements to initiate cardiovascular responses in advance of a baroreceptor-mediated response. The objective of this study was to determine whether there was an association between changes in vestibular function and cardiovascular responses during a prone-to-stand movement in astronauts after return from long-duration spaceflight.METHODS: Thirteen crewmembers who participated in International Space Station missions were tested before spaceflight and 1 d after landing. Vestibular function was evaluated by computerized dynamic posturography while their head was erect and while they performed dynamic head tilts. Heart rate and mean arterial blood pressure were measured while the subjects were in prone and standing positions.RESULTS: The 21.4% increase in the astronauts' heart rate during the prone to stand maneuver after spaceflight correlated significantly with their spaceflight-induced 48.7% decrease in postural stability during dynamic head tilts. The larger mean arterial pressure in the prone position after spaceflight compared to preflight (+7%) also correlated with the postflight decrease in postural stability during dynamic head tilts.CONCLUSION: These results indicate that an appropriate vestibular function is important to evoke optimum vestibulo-sympathetic response during orthostatically challenging voluntary movements performed after spaceflight. They also suggest that there may be a greater need to generate an anticipatory cardiovascular response after spaceflight.Deshpande N, Laurie SS, Lee SMC, Miller CA, Mulavara AP, Peters BT,Reschke MF, Stenger MB, Taylor LC, Wood SJ, Clément GR, Bloomberg JJ. Vestibular and cardiovascular responses after long-duration spaceflight. Aerosp Med Hum Perform. 2020; 91(8):621-627.

Vestibular, locomotor, and vestibulo-autonomic research: 50 years of collaboration with Bernard Cohen.

My collaboration on the vestibulo-ocular reflex with Bernard Cohen began in 1972. Until 2017, this collaboration included studies of saccades, quick phases of nystagmus, the introduction of the concept of velocity storage, the relationship of velocity storage to motion sickness, primate and human locomotion, and studies of vasovagal syncope. These studies have elucidated the functioning of the vestibuloocular reflex, the locomotor system, the functioning of the vestibulo-sympathetic reflex, and how blood pressure and heart rate are controlled by the vestibular system. Although it is virtually impossible to review all the contributions in detail in a single paper, this article traces a thread of modeling that I brought to the collaboration, which, coupled with Bernie Cohen's expertise in vestibular and sensory-motor physiology and clinical insights, has broadened our understanding of the role of the vestibular system in a wide range of sensory-motor systems. Specifically, the paper traces how the concept of a relaxation oscillator was used to model the slow and rapid phases of ocular nystagmus. Velocity information that drives the slow compensatory eye movements was used to activate the saccadic system that resets the eyes, giving rise to the relaxation oscillator properties and simulated nystagmus as well as predicting the types of unit activity that generated saccades and nystagmic beats. The slow compensatory component of ocular nystagmus was studied in depth and gave rise to the idea that there was a velocity storage mechanism or integrator that not only is a focus for visual-vestibular interaction but also codes spatial orientation relative to gravity as referenced by the otoliths. Velocity storage also contributes to motion sickness when there are visual-vestibular as well as orientation mismatches in velocity storage. The relaxation oscillator concept was subsequently used to model the stance and swing phases of locomotion, how this impacted head and eye movements to maintain gaze in the direction of body motion, and how these were affected by Parkinson's disease. Finally, the relaxation oscillator was used to elucidate the functional form of the systolic and diastolic beats during blood pressure and how vasovagal syncope might be initiated by cerebellar-vestibular malfunction.

Nondestructive and objective assessment of the vestibular function in rodent models: A review

The normal function of the vestibular system is crucial for the sense of balance. The techniques used to assess the vestibular function plays a vital role in the research of the vestibular system. In this article, we have systematically reviewed some popular methods employing vestibular reflexes and vestibular evoked potentials for assessing the vestibular function in rodent models. These vestibular reflexes and vestibular evoked potentials to effective stimuli have been used as nondestructive and objective functional measures.The main types of vestibular reflexes include the vestibulo-ocular reflex (VOR), vestibulocollic reflex (VCR), and vestibulo-sympathetic reflex (VSR). They are all capable of indicating the functions of the semicircular canals and otoliths. However, the VOR assessment is much more prevalently used because of the relatively stereotypical inputoutput relationship and simple motion pattern of the ocular response. In contrast, the complicated motion pattern and small gain of the VCR response, as well as the undesired component possibly contributed from the acceleration receptors outside the labyrinths in the VSR response, restrict the widespread applications of VCR and VSR in the assessment of the vestibular system. The vestibular evoked myogenic potentials (VEMPs) and vestibular sensory evoked potentials (VsEPs) are the two typical evoked potentials that have been also employed for evaluating the vestibular function. Through exploiting different types of the VEMPs, the saccular and utricular functions can be evaluated separately. The sound-induced VEMPs, moreover, are capable of noninvasively assessing the unilateral vestibular function. The VsEPs, via the morphology of their signal waveforms, enable the access to the location-specific information that indicates the functional statuses of different components within the vestibular neural pathway.

Vestibulo-sympathetic reflex in patients with bilateral vestibular loss

This study assessed cardiovascular control during head-down neck flexion (HDNF) in a group of patients suffering from total bilateral idiopathic vestibular loss (BVL) for 7 ± 2 yr. Nine adult patients (age 54 ± 6 yr) with BVL were recruited. Calf blood flow (CBF), mean arterial pressure (MAP), and heart rate (HR) were measured with subjects' eyes closed in two lying body positions: ventral prone (VP) and lateral (LP) on the left side. Vascular resistance (CVR) was calculated as MAP/CBF. The HDNF protocol consisted in passively changing the head position: head up (HU)-head down (HD)-HU. Measurements were taken twice at each head position. In VP CBF significantly decreased in HD (3.65 ± 0.65 mL·min-1·100 mL-1) vs. HU (4.64 ± 0.71 mL·min-1·100 mL-1) (P < 0.002), whereas CVR in VP significantly rose in HD (31.87 ± 6.93 arbitrary units) vs. HU (25.61 ± 6.36 arbitrary units) (P < 0.01). In LP no change in CBF or CVR was found between the two head positions. MAP and HR presented no difference between HU and HD in both body positions. Age of patients did not significantly affect the results. The decrease in CBF of the BVL patients was similar to the decrease observed with the same HDNF protocol in normal subjects. This suggests a sensory compensation for the lost vestibular inputs that could originate from the integration of inputs from trunk graviceptors and proprioceptive and cutaneous receptors. Another possibility is that the HDNF vascular effect is evoked mostly by nonlabyrinthine sensors.NEW & NOTEWORTHY The so-called vestibulo-sympathetic reflex, as demonstrated by the head-down neck flexion (HDNF) protocol, is present in patients with total bilateral vestibular idiopathic loss, equally in young and old subjects. The origin of the sympathetic effect of HDNF is questioned. Moreover, the physiological significance of the vestibulo-sympathetic reflex remains obscure, because it acts in opposition to the orthostatic baroreflex. It may serve to inhibit the excessively powerful baroreflex.

Hypergravity-induced plastic alteration of the vestibulo-sympathetic reflex involves decrease in responsiveness of CAMK2-expressing neurons in the vestibular nuclear complex

The vestibular system contributes to not only eye movement and posture but also the sympathetic response. Plastic alteration of the vestibulo-sympathetic reflex is induced by hypergravity load; however, the mechanism remains unknown. Here, we examined 2 g-induced changing in responsiveness of CAMK2-expressing neurons in the vestibular nucleus complex using optogenetic tools. The excitatory photostimulation of the CAMK2-expressing neurons in the unilateral vestibular nuclear complex induced body tilt to the contralateral side, while inhibitory photostimulation showed the opposite response. Photoactivation of either cell body or the axonal terminal in the rostral ventrolateral medulla showed sympathoexcitation followed by the pressor response. Furthermore, this response was significantly attenuated (49.8 ± 4%) after the 1st day of 2 g loading, and this value was further reduced by the 5th day (22.4 ± 3%), suggesting that 2 g-induced attenuation of the vestibulo-sympathetic reflex involves at least decrease in responsiveness of CAMK2-expressing neurons in the vestibular nuclear complex.

Role of peripheral vestibular receptors in the control of blood pressure following hypotension.

Hypotension is one of the potential causes of dizziness. In this review, we summarize the studies published in recent years about the electrophysiological and pharmacological mechanisms of hypotension-induced dizziness and the role of the vestibular system in the control of blood pressure in response to hypotension. It is postulated that ischemic excitation of the peripheral vestibular hair cells as a result of a reduction in blood flow to the inner ear following hypotension leads to excitation of the central vestibular nuclei, which in turn may produce dizziness after hypotension. In addition, excitation of the vestibular nuclei following hypotension elicits the vestibulosympathetic reflex, and the reflex then regulates blood pressure by a dual-control (neurogenic and humoral control) mechanism. In fact, recent studies have shown that peripheral vestibular receptors play a role in the control of blood pressure through neural reflex pathways. This review illustrates the dual-control mechanism of peripheral vestibular receptors in the regulation of blood pressure following hypotension.

Cross-coupling vestibular stimulation: motion sickness and the vestibulo-sympathetic reflex.

Motion sickness is associated with a variety of autonomic symptoms, presumably due to proximity or functional interconnectivity between the autonomic centers in the brainstem and the vestibular system. A direct influence of the vestibular system on cardiovascular variables, defined as the vestibulo-sympathetic reflex, has been reported previously. Our aim was to investigate the sudomotor components of the autonomic responses associated with motion sickness during passive cross-coupling stimulation ("roll while rotating"). Healthy subjects (n=17) were rotated at 40°/s around an earth-vertical yaw axis alone and in combination with sinusoidal roll oscillations (0.2Hz). Motion sickness was assessed verbally every minute using a 1-10 scale, while recording DC and AC skin conductance levels (SCL) from the forehead. Yaw rotation alone provoked neither motion sickness nor variations of forehead sweating. Yet during cross-coupling stimulation all subjects reported motion sickness. Higher motion sickness scores (>5) were associated with significantly higher amplitudes of AC-SCL events compared to the lower scores (0.22±0.01 vs. 0.11±0.01µS, respectively). Frequency domain analysis of the AC-SCL events revealed a peak at 0.2Hz, coinciding with the frequency of the chair rolls. The total power of AC-SCL signals did not match the trend of motion sickness scores across conditions. We conclude that: (1) although SCL is related to motion sickness, it does not follow the perceived sickness closely; (2) the discrepancy between SCL and motion sickness and the rhythmic AC-SCL events could reflect a sudomotor component of the vestibulo-sympathetic reflex.

Vestibular Activation Habituates the Vasovagal Response in the Rat.

Vasovagal syncope is a significant medical problem without effective therapy, postulated to be related to a collapse of baroreflex function. While some studies have shown that repeated static tilts can block vasovagal syncope, this was not found in other studies. Using anesthetized, male Long–Evans rats that were highly susceptible to generation of vasovagal responses, we found that repeated activation of the vestibulosympathetic reflex (VSR) with ±2 and ±3 mA, 0.025 Hz sinusoidal galvanic vestibular stimulation (sGVS) caused incremental changes in blood pressure (BP) and heart rate (HR) that blocked further generation of vasovagal responses. Initially, BP and HR fell ≈20–50 mmHg and ≈20–50 beats/min (bpm) into a vasovagal response when stimulated with Sgv\\S in susceptible rats. As the rats were continually stimulated, HR initially rose to counteract the fall in BP; then the increase in HR became more substantial and long lasting, effectively opposing the fall in BP. Finally, the vestibular stimuli simply caused an increase in BP, the normal sequence following activation of the VSR. Concurrently, habituation caused disappearance of the low-frequency (0.025 and 0.05 Hz) oscillations in BP and HR that must be present when vasovagal responses are induced. Habituation also produced significant increases in baroreflex sensitivity (p < 0.001). Thus, repeated low-frequency activation of the VSR resulted in a reduction and loss of susceptibility to development of vasovagal responses in rats that were previously highly susceptible. We posit that reactivation of the baroreflex, which is depressed by anesthesia and the disappearance of low-frequency oscillations in BP and HR are likely to be critically involved in producing resistance to the development of vasovagal responses. SGVS has been widely used to activate muscle sympathetic nerve activity in humans and is safe and well tolerated. Potentially, it could be used to produce similar habituation of vasovagal syncope in humans.

Dual control of the vestibulosympathetic reflex following hypotension in rats

Orthostatic hypotension (OH) is associated with symptoms including headache, dizziness, and syncope. The incidence of OH increases with age. Attenuation of the vestibulosympathetic reflex (VSR) is also associated with an increased incidence of OH. In order to understand the pathophysiology of OH, we investigated the physiological characteristics of the VSR in the disorder. We applied sodium nitroprusside (SNP) to conscious rats with sinoaortic denervation in order to induce hypotension. Expression of pERK in the intermediolateral cell column (IMC) of the T4~7 thoracic spinal regions, blood epinephrine levels, and blood pressure were evaluated following the administration of glutamate and/or SNP. SNP-induced hypotension led to increased pERK expression in the medial vestibular nucleus (MVN), rostral ventrolateral medullary nucleus (RVLM) and the IMC, as well as increased blood epinephrine levels. We co-administered either a glutamate receptor agonist or a glutamate receptor antagonist to the MVN or the RVLM. The administration of the glutamate receptor agonists, AMPA or NMDA, to the MVN or RVLM led to elevated blood pressure, increased pERK expression in the IMC, and increased blood epinephrine levels. Administration of the glutamate receptor antagonists, CNQX or MK801, to the MVN or RVLM attenuated the increased pERK expression and blood epinephrine levels caused by SNP-induced hypotension. These results suggest that two components of the pathway which maintains blood pressure are involved in the VSR induced by SNP. These are the neurogenic control of blood pressure via the RVLM and the humoral control of blood pressure via epinephrine release from the adrenal medulla.

The response of the vestibulosympathetic reflex to linear acceleration in the rat.

The vestibulosympathetic reflex (VSR) increases blood pressure (BP) upon arising to maintain blood flow to the brain. The optimal directions of VSR activation and whether changes in heart rate (HR) are associated with changes in BP are still not clear. We used manually activated pulses and oscillatory linear accelerations of 0.2-2.5 g along the naso-occipital, interaural, and dorsoventral axes in isoflurane-anesthetized, male Long-Evans rats. BP and HR were recorded with an intra-aortic sensor and acceleration with a three-dimensional accelerometer. Linear regressions of BP changes in accelerations along the upward, downward, and forward axes had slopes of ≈3-6 mmHg · g-1 (P < 0.05). Lateral and backward accelerations did not produce consistent changes in BP. Thus upward, downward, and forward translations were the directions that significantly altered BP. HR was unaffected by these translations. The VSR sensitivity to oscillatory forward-backward translations was ≈6-10 mmHg · g-1 at frequencies of ≈0.1 Hz (0.2 g), decreasing to zero at frequencies above 2 Hz (1.8 g). Upward, 70° tilts of an alert rat increased BP by 9 mmHg · g-1 without changes in HR, indicating that anesthesia had not reduced the VSR sensitivity. The similarity in BP induced in alert and anesthetized rats indicates that the VSR is relatively insensitive to levels of alertness and that the VSR is likely to cause changes in BP through modification of peripheral vascular resistance. Thus the VSR, which is directed toward the cardiovascular system, is in contrast to the responses in the alert state that can produce sweating, alterations in BP and HR, and motion sickness.

Imidazoleacetic acid-ribotide in vestibulo-sympathetic pathway neurons.

Imidazole-4-acetic acid-ribotide (IAARP) is a putative neurotransmitter/modulator and an endogenous regulator of sympathetic drive, notably systemic blood pressure, through binding to imidazoline receptors. IAARP is present in neurons and processes throughout the CNS, but is particularly prevalent in regions that are involved in blood pressure control. The goal of this study was to determine whether IAARP is present in neurons in the caudal vestibular nuclei that participate in the vestibulo-sympathetic reflex (VSR) pathway. This pathway is important in modulating blood pressure upon changes in head position with regard to gravity, as occurs when humans rise from a supine position and when quadrupeds climb or rear. Sinusoidal galvanic vestibular stimulation was used to activate the VSR and cfos gene expression in VSR pathway neurons of rats. These subjects had previously received a unilateral FluoroGold tracer injection in the rostral or caudal ventrolateral medullary region. The tracer was transported retrogradely and filled vestibular neuronal somata with direct projections to the injected region. Brainstem sections through the caudal vestibular nuclei were immunostained to visualize FluoroGold, cFos protein, IAARP and glutamate immunofluorescence. The results demonstrate that IAARP is present in vestibular neurons of the VSR pathway, where it often co-localizes with intense glutamate immunofluorescence. The co-localization of IAARP and intense glutamate immunofluorescence in VSR neurons may represent an efficient chemoanatomical configuration, allowing the vestibular system to rapidly up- and down-modulate the activity of presympathetic neurons in the ventrolateral medulla, thereby altering blood pressure.