title: Reduction of nitric oxide-mediated γ-amino butyric acid release in rostral ventrolateral medulla is involved in superoxide-induced sympathoexcitation of hypertensive rats.
abstract: 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.
  
  
  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 N(G)-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.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Shinohara
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D001640:Bicuculline / Q000008:administration & dosage; D003497:Cyclic N-Oxides / Q000008:administration & dosage; D004195:Disease Models, Animal; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D016166:Free Radical Scavengers / Q000008:administration & dosage; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage; D006339:Heart Rate; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000294:innervation*; D007736:Kynurenic Acid / Q000008:administration & dosage; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D017551:Microdialysis; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D058787:GABA-A Receptor Antagonists; D013113:Spin Labels; D013481:Superoxides; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D019001:Nitric Oxide Synthase; D007736:Kynurenic Acid; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester; D001640:Bicuculline