Dual control of the vestibulosympathetic reflex following hypotension in rats

Abstract

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.

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

“…It is postulated that hypotension activates the VSR by exciting the sympathetic nerves through the IMC in the spinal cord. Interestingly, Lu et al [ 53 ] and Park et al [ 54 ] found that hypotension increased c-Fos and pERK protein expression in the IMC of T4-T7 spinal cord in conscious rats with SAD. These findings demonstrate that hypotension increases sympathetic nerve activity through the vestibular nuclei and RVLM.…”

“…Additionally, it has been demonstrated that glutamate plays an important role in the signaling pathway underlying the transmission of neural signals from the RVLM to the IMC in response to hypotension [ 53 54 ]. In fact, pretreatment with microinjection of glutamate receptor antagonists (MK801 or CNQX) into the MVN or RVLM prevents the increase of pERK or c-Fos protein expression in the IMC after hypotension.…”

“…The adrenal medulla releases epinephrine into the bloodstream, and the released epinephrine plays an important role in the control of blood pressure. Recent studies have investigated the role of blood epinephrine in the humoral control of blood pressure [ 53 54 ]. It was found that blood epinephrine levels were elevated after hypotension, and microinjection of glutamate agonists (NMDA or AMPA) into the MVN or RVLM also increased the blood epinephrine levels.…”

“…Therefore, after hypotension, the VSR may regulate blood pressure through increased epinephrine release from the adrenal medulla, and the released epinephrine may be involved in the humoral or delayed control of blood pressure in the vestibulosympathetic reflex ( Fig. 1 ) [ 54 ].…”

“… The solid line is based on the results obtained in our studies. VNC, Vestibular nuclear complex; RVLM, Rostral ventrolateral medullary nuclei; IMC, Intermediolateral cell column of the spinal cord; AM, Adrenal medulla; NTS, Nucleus tractus solitarius; CVLM, Caudal ventrolateral medullary nucleus [ 54 with permission]. …”