Reduction of nitric oxide-mediated γ-amino butyric acid release in rostral ventrolateral medulla is involved in superoxide-induced sympathoexcitation of hypertensive rats

Keisuke Shinohara, Yoshitaka Hirooka, Takuya Kishi, Kenji Sunagawa

研究成果: ジャーナルへの寄稿学術誌査読

27 被引用数 (Scopus)

抄録

Background: The rostral ventrolateral medulla (RVLM) in the brainstem is responsible for regulation of the sympathetic nervous system. In the RVLM, nitric oxide (NO)-mediated y-amino butyric acid (GABA) is a major sympatho-inhibitory amino acid neurotransmitter and superoxide is a major sympathoexcitatory factor. In this study, we investigated whether or not NO-mediated GABA release is involved in superoxide-induced sympathoexcitation in the RVLM of hypertensive rats. Methods and Results: For our model hypertensive rats with sympathoexcitation, we used stroke-prone spontaneously hypertensive rats (SHRSP). GABA levels in the RVLM were measured by in vivo microdialysis. Microinjection of tempol, a superoxide scavenger, into the RVLM decreased arterial pressure (AP), heart rate (HR), and renal sympathetic nerve activity (RSNA) with an increase in GABA release in the RVLM. Microinjection of NG-mono-methyl-L-arginine (L-NMMA), an NO synthase inhibitor, into the RVLM increased AP, HR, and RSNA with a decrease in GABA release in the RVLM. Prior microinjection of L-NMMA into the RVLM attenuated the tempol-induced changes in AP, HR, RSNA, and GABA release in the RVLM. Microinjection of bicuculline, a GABA receptor blocker, into the RVLM attenuated the tempol- and L-NMMA-induced changes in AP, HR, and RSNA. Conclusions: The findings suggest that reduction of NO-mediated GABA release in the RVLM is partly involved in superoxide-induced sympathoexcitation of SHRSP.

本文言語英語
ページ(範囲)2814-2821
ページ数8
ジャーナルCirculation Journal
76
12
DOI
出版ステータス出版済み - 2012

!!!All Science Journal Classification (ASJC) codes

  • 循環器および心血管医学

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