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.

Pathways of Neurogenic and Humoral Control in the Vestibulosympathetic Reflex of Conscious Rats / 대한평형의학회지

OBJECTIVE: The vestibular system contributes control of blood pressure during postural changes through the vestibulosympathetic reflex. In the vestibulosympathetic reflex, afferent signals from the peripheral vestibular receptors are transmitted to the vestibular nuclei, rostral ventrolateral medullary nuclei, and then to the intermediolateral cell column of the thoracolumbar spinal cord. Physiological characteristics of the vestibulosympathetic reflex in terms of neurogenic and humoral control of blood pressure were investigated in this study. METHODS: Conscious rats with sinoaortic denervation were used for removal of baroreceptors in reflex control of blood pressure, and hypotension was induced by intravenous infusion of sodium nitroprusside (SNP). Expression of c-Fos protein was measured in the medial vestibular nuclei (MVN), rostral vestrolateral medullary nuclei(RVLM), and intermediolateral cell column (IMC) in T4-7, and levels of blood epinephrine were measured following SNP-induced hypotension. RESULTS: SNP-induced hypotension significantly increased expression of c-Fos protein in the MVN, RVLM, and IMC, also significantly increased level of blood epinephrine compared to normotensive control animals. CONCLUSION: These results suggest that the vestibulosympathetic reflex regulates blood pressure through neurogenic control including MVN, RVLM, and IMC, also through humoral control including epinephrine secretion by the adrenal medulla following SNP-induced hypotension. The physiological characteristics of the reflex may contribute to basic treatment of impairment of blood pressure control during postural changes.

Analysis of the Baroreceptor and Vestibular Receptor Inputs in the Rostral Ventrolateral Medulla following Hypotension in Conscious Rats

Input signals originating from baroreceptors and vestibular receptors are integrated in the rostral ventrolateral medulla (RVLM) to maintain blood pressure during postural movement. The contribution of baroreceptors and vestibular receptors in the maintenance of blood pressure following hypotension were quantitatively analyzed by measuring phosphorylated extracellular regulated protein kinase (pERK) expression and glutamate release in the RVLM. The expression of pERK and glutamate release in the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or sinoaortic denervation (SAD) following hypotension induced by a sodium nitroprusside (SNP) infusion. The expression of pERK was significantly increased in the RVLM in the control group following SNP infusion, and expression peaked 10 min after SNP infusion. The number of pERK positive neurons increased following SNP infusion in BL, SAD, and BL+SAD groups, although the increase was smaller than seen in the control group. The SAD group showed a relatively higher reduction in pERK expression when compared with the BL group. The level of glutamate release was significantly increased in the RVLM in control, BL, SAD groups following SNP infusion, and this peaked 10 min after SNP infusion. The SAD group showed a relatively higher reduction in glutamate release when compared with the BL group. These results suggest that the baroreceptors are more powerful in pERK expression and glutamate release in the RVLM following hypotension than the vestibular receptors, but the vestibular receptors still have an important role in the RVLM.

Effect of Glutamate on the Vestibulo-Solitary Projection after Sodium Nitroprusside-Induced Hypotension in Conscious Rats

Orthostatic hypotension is most common in elderly people, and its prevalence increases with age. Attenuation of the vestibulo-sympathetic reflex (VSR) is commonly associated with orthostatic hypotension. In this study, we investigated the role of glutamate on the vestibulo-solitary projection of the VSR pathway to clarify the pathophysiology of orthostatic hypotension. Blood pressure and expression of both pERK and c-Fos protein were evaluated in the nucleus tractus solitarius (NTS) after microinjection of glutamate into the medial vestibular nucleus (MVN) in conscious rats with sodium nitroprusside (SNP)-induced hypotension that received baroreceptor unloading via sinoaortic denervation (SAD). SNP-induced hypotension increased the expression of both pERK and c-Fos protein in the NTS, which was abolished by pretreatment with glutamate receptor antagonists (MK801 or CNQX) in the MVN. Microinjection of glutamate receptor agonists (NMDA or AMPA) into the MVN increased the expression of both pERK and c-Fos protein in the NTS without causing changes in blood pressure. These results indicate that both NMDA and AMPA receptors play a significant role in the vestibulo-solitary projection of the VSR pathway for maintaining blood pressure, and that glutamatergic transmission in this projection might play a key role in the pathophysiology of orthostatic hypotension.

Additive Role of the Vestibular End Organ and Baroreceptors on the Regulation of Blood Pressure in Rats

Contribution of the vestibular end organ to regulation of arterial pressure was quantitatively compared with the role of baroreceptors in terms of baroreflex sensitivity and c-Fos protein expression in the rostral ventrolateral medulla (RVLM). Baroreflex sensitivity and c-Fos protein expression in the RVLM were measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or baroreceptor unloading. BL attenuated baroreflex sensitivity during intravenous infusion of sodium nitroprusside (SNP), but did not significantly affect the sensitivity following infusion of phenylephrine (PE). Baroreflex sensitivity became positive following sinoaortic denervation (SAD) during infusion of PE and attenuated sensitivity during infusion of SNP. Baroreflex sensitivity also became positive following double ablation (BL+SAD) during infusion of PE, and attenuated sensitivity during infusion of SNP. c-Fos protein expression increased significantly in the RVLM in the sham group after SNP administration. However, the BL, SAD, and SAD+BL groups showed significant decreases in c-Fos protein expression compared with that in the sham group. The SAD group showed more reduced c-Fos protein expression than that in the BL group, and the SAD+BL group showed less expression than that in the SAD group. These results suggest that the vestibular system cooperates with baroreceptors to maintain arterial pressure during hypotension but that baroreceptors regulate arterial pressure during both hypotension and hypertension. Additionally, afferent signals for maintaining blood pressure from the vestibular end organs and the baroreceptors may be integrated in the RVLM.

The Effects of Glutamate NMDA Receptor Antagonist MK-801 on Gastrointestinal Motility after Middle Cerebral Artery Occlusion in Rats

This study was performed to investigate the role of glutamate neurotransmitter system on gastrointestinal motility in a middle cerebral artery occlusion (MCAO) model of rats. The right middle cerebral artery was occluded by surgical operation, and intestinal transit and geometric center as a parameter of gastrointestinal motility and expression of c-Fos protein in the insular cortex and cingulate cortex were measured at 2 and 12 h after MCAO. Intestinal transit was 66.3+/-7.5% and 62.3+/-5.7% 2 and 12 h after sham operation, respectively, and MCAO significantly decreased intestinal transit to 39.0+/-3.5% and 47.0+/-5.1% at 2 and 12 h after the occlusion, respectively (p<0.01). The geometric center was 5.6+/-0.4 and 5.2+/-0.9 at 2 and 12 h after sham operation, respectively, and MCAO significantly decreased geometric center to 2.9+/-0.8 and 3.0+/-0.3 at 2 and 12 h after the occlusion, respectively (p<0.01). In control animals, injection of atropine decreased intestinal transit to 35.9+/-5.2%, and injection of glutamate NMDA receptor antagonist, MK-801, decreased intestinal transit to 28.8+/-9.5%. Pretreatment with MK-801, a glutamate NMDA receptor antagonist, in the MCAO group decreased intestinal transit to 11.8+/-3.2%, which was significantly decreased compared to MCAO group (p<0.01). MCAO markedly increased the expression of c-Fos protein in the insular cortex and cingulate cortex ipsilateral to the occlusion 2 h after MCAO, and pretreatment with MK-801 produced marked reduction of c-Fos protein expression compared to MCAO group (p<0.01). These results suggest that modulation of gastrointestinal motility after MCAO might be partially mediated through a glutamate NMDA receptor system.

c-fos mRNA Expression in the Vestibular System following Hypergravity Stimulation in Rats

Altered environmental gravity, including both hypo- and hypergravity, may result in space adaptation syndrome. To explore the characteristics of this adaptive plasticity, the expression of immediate early gene c-fos mRNA in the vestibular related tissues following an exposure to hypergravity stimulus was determined in rats. The animals were subjected to a force of 2 g (twice earth's gravity) for 1, 3, or 12 h, and were examined poststimulus at 0, 2, 6, 12, and 24 h. RT-PCR (reverse transcription polymerase chain reaction) and real-time quantitative RT-PCR were adopted to analyze temporal changes in the expression of c-fos mRNA. The hypergravity stimulus increased the expression of c-fos mRNA in the vestibular ganglion, medial vestibular nucleus, inferior vestibular nucleus, hippocampus, cerebellum, and cortex. The peak expression occurred at 0 h poststimulation in animals stimulated with hypergravity for 1 h, and at 6 h poststimulus in those stimulated for 3 h. In contrast, those stimulated for 12 h exhibited dual peaks at 0 and 12 h poststimulus. Bilateral labyrinthectomy markedly attenuated the degree of c-fos mRNA expression. Glutamate receptor antagonist also dramatically attenuated the degree of c-fos mRNA expression. These results indicate that expression of c-fos mRNA in response to hypergravity occurs in the vestibular related tissues of the central nervous system, in which peripheral vestibular receptors and glutamate receptors play an important role. The temporal pattern of c-fos mRNA expression depended on the duration of the hypergravity stimulus.

Role of Central Vestibular Pathway on Control of Blood Pressure During Acute Hypotension in Rats

BACKGROUND AND OBJECTIVES: Central role of the vestibular system on control of blood pressure and interrelationships between the vestibular nucleus and solitary nucleus during acute hypotension were investigated in bilateral labyrinthectomized (BLX) or sinoaortic denervated (SAD) rats. Changes of electrical activity in the medial vestibular nucleus (MVN), solitary tract nucleus (STN), and rostral ventrolateral medullary nucleus (RVLM) were investigated in rats in while acute hypotension was induced by sodium nitroprusside (SNP). RESULTS: Evoked potential in MVN neuron caused by electrical stimulation of the peripheral vestibular system was composed of 3 waves with latencies of 0.48+/-.10 ms, 1.04+/-.09 ms and 1.98+/-.19 ms. Electrical stimulation to MVN or RVLM increased blood pressure. MVN at the induction of acute hypotension showed excitation in 61% of type I neurons and inhibition in 68% of type II neurons. In STN, acute hypotension produced excitation in 62.1% of neurons recorded in intact labyrinthine animals, inhibition in 72.3% of neurons recorded in BL animals, and excitation in 60% of recorded neurons in SAD animals. In RVLM, acute hypotension produced excitation in 66.7% of neurons recorded in intact labyrinthine animals and inhibition in 64.9% of neurons recorded in BL animals. In spatial distribution of STN neurons responded to acute hypotension, excitatory responses were mainly recorded in rostral and ventral portion, and inhibitory responses were mainly recorded in caudal and lateral portion. In RVLM, excitatory responses were mainly recorded in rostral and dorsomedial portion, and inhibitory responses were mainly recorded in caudal and ventrolateral portion. CONCLUSION: These results suggest that afferent signals from the peripheral vestibular receptors are transmitted to STN through the vestibular nuclei and assist to the baroreceptors for controlling blood pressure following acute hypotension.