Reduction of Nitric Oxide-Mediated γ-Amino Butyric Acid Release in Rostral Ventrolateral Medulla Is Involved in Superoxide-Induced Sympathoexcitation of Hypertensive Rats

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  • Shinohara Keisuke
    Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences
  • Hirooka Yoshitaka
    Department of Advanced Cardiovascular Regulation and Therapeutics, Kyushu University Graduate School of Medical Sciences
  • Kishi Takuya
    Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu University Graduate School of Medical Sciences
  • Sunagawa Kenji
    Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences

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  • Reduction of Nitric Oxide-Mediated γ-Amino Butyric Acid Release in Rostral Ventrolateral Medulla Is Involved in Superoxide-Induced Sympathoexcitation of Hypertensive Rats

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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 γ-amino butyric acid (GABA) is a major sympathoinhibitory 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-monomethyl-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.  (Circ J 2012; 76: 2814–2821)<br>

収録刊行物

  • Circulation Journal

    Circulation Journal 76 (12), 2814-2821, 2012

    一般社団法人 日本循環器学会

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