Inhibition of glial glutamate transporter GLT1 in the nucleus of the solitary tract attenuates baroreflex control of sympathetic nerve activity and heart rate

Kenta Yamamoto, Steve Mifflin

Research output: Contribution to journalArticle

Abstract

The astrocytic glutamate transporter (GLT1) plays an important role in the maintenance of extracellular glutamate concentration below neurotoxic levels in brain. However, the functional role of GLT1 within the nucleus of the solitary tract (NTS) in the regulation of cardiovascular function remains unclear. We examined the effect of inhibiting GLT1 in the subpostremal NTS on mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA) and heart rate (HR) in anesthetized, artificially ventilated rats. It was found that dihydrokainate (DHK; inhibitor of GLT1, 5 mmol/L, 100 nL) injections into the NTS (n = 6) decreased MAP (50 ± 10 mmHg, mean ± SD), RSNA (89 ± 14%) and HR (37 ± 6 bpm). Pretreatment with kynurenate (KYN; glutamate receptor antagonist, 5 mmol/L, 30 μL) topically applied to the dorsal surface of the brainstem (n = 4) attenuated the responses to NTS injections of DHK (P < 0.01). The effect of DHK on arterial baroreflex function was examined using i.v. infusions of phenylephrine and nitroprusside. DHK reduced baroreflex response range (maximum−minimum) of RSNA by 91 ± 2% and HR by 83 ± 5% (n = 6, P < 0.001). These results indicate that inhibition of GLT1 within the NTS decreases MAP, RSNA, and HR by the activation of ionotropic glutamate receptors. As a result, baroreflex control of RSNA and HR was dramatically attenuated. The astrocytic glutamate transporter in the NTS plays an important role in the maintenance and regulation of cardiovascular function.

Original languageEnglish
Article numbere13877
JournalPhysiological Reports
Volume6
Issue number18
DOIs
StatePublished - Sep 2018

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Amino Acid Transport System X-AG
Solitary Nucleus
Baroreflex
Neuroglia
Heart Rate
Kidney
Arterial Pressure
Maintenance
Kynurenic Acid
Ionotropic Glutamate Receptors
Excitatory Amino Acid Antagonists
Injections
Nitroprusside
Phenylephrine
Brain Stem
Glutamic Acid
Brain

Keywords

  • Astrocytes
  • NTS
  • baroreflex
  • glutamate transporter

Cite this

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abstract = "The astrocytic glutamate transporter (GLT1) plays an important role in the maintenance of extracellular glutamate concentration below neurotoxic levels in brain. However, the functional role of GLT1 within the nucleus of the solitary tract (NTS) in the regulation of cardiovascular function remains unclear. We examined the effect of inhibiting GLT1 in the subpostremal NTS on mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA) and heart rate (HR) in anesthetized, artificially ventilated rats. It was found that dihydrokainate (DHK; inhibitor of GLT1, 5 mmol/L, 100 nL) injections into the NTS (n = 6) decreased MAP (50 ± 10 mmHg, mean ± SD), RSNA (89 ± 14{\%}) and HR (37 ± 6 bpm). Pretreatment with kynurenate (KYN; glutamate receptor antagonist, 5 mmol/L, 30 μL) topically applied to the dorsal surface of the brainstem (n = 4) attenuated the responses to NTS injections of DHK (P < 0.01). The effect of DHK on arterial baroreflex function was examined using i.v. infusions of phenylephrine and nitroprusside. DHK reduced baroreflex response range (maximum−minimum) of RSNA by 91 ± 2{\%} and HR by 83 ± 5{\%} (n = 6, P < 0.001). These results indicate that inhibition of GLT1 within the NTS decreases MAP, RSNA, and HR by the activation of ionotropic glutamate receptors. As a result, baroreflex control of RSNA and HR was dramatically attenuated. The astrocytic glutamate transporter in the NTS plays an important role in the maintenance and regulation of cardiovascular function.",
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Inhibition of glial glutamate transporter GLT1 in the nucleus of the solitary tract attenuates baroreflex control of sympathetic nerve activity and heart rate. / Yamamoto, Kenta; Mifflin, Steve.

In: Physiological Reports, Vol. 6, No. 18, e13877, 09.2018.

Research output: Contribution to journalArticle

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T1 - Inhibition of glial glutamate transporter GLT1 in the nucleus of the solitary tract attenuates baroreflex control of sympathetic nerve activity and heart rate

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