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.

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.

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.

Comparative analysis of vestibular receptor and baroreceptor inputs to the nucleus tractus solitarius following acute hypotension in conscious rats.

Blood pressure is maintained by the interaction between the arterial baroreflexes and the vestibulo-cardiovascular reflexes during postural changes. In this study, the influence of the vestibular receptors on the maintenance of blood pressure following acute hypotension was quantitatively compared with the role of baroreceptors in terms of c-Fos protein expression in the nucleus tractus solitarius (NTS). Expression of c-Fos protein in the NTS was measured in conscious rats that had undergone bilateral labyrinthectomy (BL) and/or sinoaortic denervation (SAD). Expression of c-Fos protein increased significantly in the NTS in the sham group after sodium nitroprusside (SNP) administration. However, the BL, SAD, and SAD+BL groups showed significant decreases in c-Fos protein expression compared to that of the sham group. The SAD group showed relatively more reduction in c-Fos protein expression than the BL group, and the SAD+BL group showed the least expression among the three experimental groups. The c-Fos protein expression in the NTS following acute hypotension was localized to the caudal portions of the nuclei in the BL and SAD groups. These results suggest that the role of vestibular receptors in maintaining blood pressure following acute hypotension is less potent than that of the baroreceptors but more potent than other afferent inputs in conscious rats. In addition, afferent signals for maintaining blood pressure originating from the vestibular receptors and the baroreceptors may converge in the caudal portion of the NTS.

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.

Mechanism of glutamate receptor for excitation of medial vestibular nucleus induced by acute hypotension.

In the vestibular nuclei, acute hypotension induces excitation of electrical activity and expression of c-Fos protein and phosphorylated extracellular signal-regulated kinase (pERK). Expression of c-Fos protein and pERK is mediated by the excitatory neurotransmitter, glutamate. We investigated the signaling pathway of glutamate and its receptors in the vestibular nuclei following acute hypotension in conscious rats. Glutamate release and the expression of c-Fos protein in the medial vestibular nuclei (MVN) were measured by microdialysis and immunohistochemical analysis, respectively. We compared the responses of rats with unilateral labyrinthectomy to unaltered controls. Acute hypotension was induced by infusing sodium nitroprusside (SNP) into the femoral vein. In the control group, glutamate release and the expression of c-Fos protein increased in the bilateral MVN following acute hypotension. In the unilateral labyrinthectomy group, glutamate release and the expression of c-Fos protein increased in the MVN contralateral to the lesion, but did not change in the ipsilateral MVN following acute hypotension. Microinjection of NMDA or AMPA into the lateral ventricle increased the expression of c-Fos protein in the bilateral MVN of conscious intact labyrinthine rats. However, after intracerebroventricular microinjection of MK-801 or CNQX little c-Fos protein was expressed in the bilateral MVN of these rats following acute hypotension. These results suggest that in response to acute hypotension, excitatory afferent signals from the peripheral vestibular receptors release glutamate into postsynaptic neurons in the vestibular nuclei. These excitatory signals are transmitted through the NMDA receptors and AMPA receptors of glutamate in the vestibular system.

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.