Inhibition of Rho-kinase in the nucleus tractus solitarius enhances glutamate sensitivity in rats

Koji Ito, Yoshitaka Hirooka, Nobuaki Hori, Yoshikuni Kimura, Yoji Sagara, Hiroaki Shimokawa, Akira Takeshita, Kenji Sunagawa

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

The Rho/Rho-kinase pathway in the central nervous system is involved in the maintenance of dendritic spines, which form the postsynaptic contact sites of excitatory synapses. Inhibition of the Rho-kinase pathway in neuron promotes dendritic spines or branches. In contrast, activation of the Rho/Rho-kinase pathway reduces dendritic spines or branches. Recent studies suggest that morphological changes of dendritic spines occur rapidly, and spine morphology is associated with glutamate sensitivity. The aim of the present study was to determine whether Rho-kinase activity affects glutamate sensitivity in the nucleus tractus solitarii (NTS) of Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). We first examined the effects of unilateral glutamate injection in the NTS. There was a significantly smaller decrease in arterial pressure in SHR than in WKY. We then examined the depressor responses evoked by unilateral glutamate injection into the NTS after preinjection of Y-27632, a specific Rho-kinase inhibitor. Preinjection of Y-27632 enhanced the glutamate response in both strains. However, the magnitude of the augmentation was significantly greater in SHR than in WKY. Furthermore, we recorded single-unit activity of NTS neurons from medulla brain slice preparations. N-methyl-D-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4- isoxazolepropionate (AMPA) was applied iontophoretically to the recorded neurons, and neuronal activity was recorded before and after Y-27632 perfusion. Y-27632 perfusion increased the response to NMDA and AMPA. These results suggest that inhibition of Rho-kinase activity in the NTS enhances glutamate sensitivity in WKY and SHR and might improve impaired glutamate sensitivity in SHR.

Original languageEnglish
Pages (from-to)360-365
Number of pages6
JournalHypertension
Volume46
Issue number2
DOIs
Publication statusPublished - 2005 Aug

Keywords

  • Amino acid
  • Autonomic nervous system
  • Blood pressure
  • Central nervous system
  • Rats, spontaneously hypertensive

ASJC Scopus subject areas

  • Internal Medicine

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