Korean J Physiol Pharmacol.  2015 May;19(3):275-281. 10.4196/kjpp.2015.19.3.275.

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

• Li LW
• Jin GS
• Yang YZ
• Ameer AN
• Kim MS
• Park BR
• Jin YZ

• KMID: 1791430
• DOI: http://doi.org/10.4196/kjpp.2015.19.3.275

Abstract

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.

Keyword

c-Fos protein; Glutamate; Nucleus tractus solitarius; Orthostatic hypotension; Vestibulosympathetic reflex

MeSH Terms

Aged
Animals
Blood Pressure
Denervation
Excitatory Amino Acid Antagonists
Glutamic Acid*
Humans
Hypotension*
Hypotension, Orthostatic
Microinjections
N-Methylaspartate
Nitroprusside
Pressoreceptors
Prevalence
Rats*
Receptors, AMPA
Receptors, Glutamate
Reflex
Sodium*
Solitary Nucleus
Vestibular Nuclei
Excitatory Amino Acid Antagonists
Glutamic Acid
N-Methylaspartate
Nitroprusside
Receptors, AMPA
Receptors, Glutamate
Sodium

Figure

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  Fig. 1 Changes in blood pressure after microinjection of glutamate receptor antagonists or agonists into the medial vestibular nuclei (MVN). (A) Effect of pretreatment with glutamate receptor antagonists on SNP-induced hypotension. Intravenous infusion of SNP (15 µg·kg-1·min-1) reduced blood pressure. Pretreatment with artificial cerebrospinal fluid (ACSF), lidocaine (Lido), or the glutamate receptor antagonist MK801 or CNQX in the MVN did not abolish SNP-induced hypotension. (B) Effect of glutamate receptor agonists on blood pressure. Microinjection of ACSF or the glutamate receptor agonist NMDA or AMPA into the MVN had no effect on changes in blood pressure.

• 

  Fig. 2 Photomicrographs showing the effect of glutamate on pERK expression in the nucleus tractus solitarius (NTS). (A) Effect of pretreatment with glutamate receptor antagonists on pERK expression in the NTS. SNP-induced hypotension after pretreatment with artificial cerebrospinal fluid (ACSF) increased pERK expression in the NTS. Pretreatment with lidocaine or the glutamate receptor antagonist MK801 or CNQX in the MVN attenuated pERK expression in the NTS caused by SNP infusion. ACSF+SNP, SNP infusion after pretreatment with ACSF in the MVN; Lido+SNP, SNP infusion after pretreatment with lidocaine in the MVN; MK801+SNP, SNP infusion after pretreatment with MK801 in the MVN; CNQX+SNP, SNP infusion after pretreatment with CNQX in the MVN. Rectangle represents higher magnification of the NTS. (B) Effect of glutamate receptor agonists on pERK expression in the NTS. Microinjection of the glutamate receptor agonist NMDA or AMPA into the MVN increased pERK expression in the NTS. pERK expression was measured 10 min after SNP infusion or microinjection of glutamate agonist into the MVN. ACSF, microinjection of ACSF into the MVN; NMDA, microinjection of NMDA into the MVN; AMPA, microinjection of AMPA into the MVN. NTS, nucleus tractus solitarius (the coordinate: 0.2 mm rostral to the obex). Scale bar=200 µm. In right upper quadrant of B, a and b represent higher magnification of the NTS in NMDA and AMPA, respectively (Scale bar=50 µm).

• 

  Fig. 3 Bar histograms showing the effect of glutamate on pERK expression in the nucleus tractus solitarius. ACSF+SNP, SNP infusion after pretreatment with ACSF in the MVN; Lido+SNP, SNP infusion after pretreatment with lidocaine in the MVN; MK801+SNP, SNP infusion after pretreatment with MK801 in the MVN; CNQX+SNP, SNP infusion after pretreatment with CNQX in the MVN; ACSF, microinjection of ACSF into the MVN; NMDA, microinjection of NMDA into the MVN; AMPA, microinjection of AMPA into the MVN. The number of animals in each group was six. Values are mean±SD. *Significant difference from ACSF+SNP group (**p<0.01). †Significant difference from ACSF group (‡p<0.01).

• 

  Fig. 4 Photomicrographs showing the effect of glutamate on c-Fos protein expression in the nucleus tractus solitarius (NTS). (A) Effect of pretreatment with glutamate receptor antagonists on c-Fos protein expression in the NTS. SNP-induced hypotension after pretreatment with artificial cerebrospinal fluid (ACSF) increased c-Fos protein expression in the NTS. Pretreatment with lidocaine or the glutamate antagonist MK801 or CNQX in the MVN attenuated c-Fos protein expression in the NTS caused by SNP infusion. ACSF+SNP, SNP infusion after pretreatment with ACSF in the MVN; Lido+SNP, SNP infusion after pretreatment with lidocaine in the MVN; MK801+SNP, SNP infusion after pretreatment with MK801 in the MVN; CNQX+SNP, SNP infusion after pretreatment with CNQX in the MVN. Rectangle represents higher magnification of the NTS. (B) Effect of glutamate receptor agonists on c-Fos protein expression in the NTS. Microinjection of the glutamate agonist NMDA or AMPA into the MVN increased c-Fos protein expression in the NTS. c-Fos protein expression was measured 90 min after SNP infusion or microinjection of glutamate agonist into the MVN. ACSF, microinjection of ACSF into the MVN; NMDA, microinjection of NMDA into the MVN; AMPA, microinjection of AMPA into the MVN. NTS, nucleus tractus solitarius (the coordinate: 0.2 mm rostral to the obex). Scale bar=200 µm. In right upper quadrant of B, a and b represent higher magnification of the NTS in NMDA and AMPA, respectively (Scale bar=50 µm).

• 

  Fig. 5 Bar histograms showing the effect of glutamate on c-Fos protein expression in the nucleus tractus solitarius. ACSF+SNP, SNP infusion after pretreatment with ACSF in the MVN; Lido+SNP, SNP infusion after pretreatment with lidocaine in the MVN; MK801+SNP, SNP infusion after pretreatment with MK801 in the MVN; CNQX+SNP, SNP infusion after pretreatment with CNQX in the MVN; ACSF, microinjection of ACSF into the MVN; NMDA, microinjection of NMDA into the MVN; AMPA, microinjection of AMPA into the MVN. The number of animals in each group was six. Values are mean±SD. *Significant difference from ACSF+SNP group (**p<0.01). †Significant difference from ACSF group (‡p<0.01).

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