title: Increased reactive oxygen species in rostral ventrolateral medulla contribute to neural mechanisms of hypertension in stroke-prone spontaneously hypertensive rats.
abstract: BACKGROUND
  Oxidative stress increases in hypertension. The aim of this study was to determine whether reactive oxygen species (ROS) are increased in the rostral ventrolateral medulla (RVLM) in the brainstem, where the vasomotor center is located, in stroke-prone spontaneously hypertensive rats (SHRSP), and, if so, to determine whether the increased ROS contribute to neural mechanisms of hypertension in SHRSP.
  
  
  RESULTS
  We measured ROS levels in the RVLM of SHRSP and compared them with those in Wistar-Kyoto rats (WKY). Thiobarbituric acid-reactive substances were increased in SHRSP compared with WKY. ROS were measured by electron spin resonance (ESR) spectroscopy. The ESR signal decay rate in the RVLM of SHRSP was significantly increased compared with that in WKY, and this increase was abolished by dimethylthiourea (a hydroxyl radical scavenger). The increased ESR signal decay rate was reduced to the same extent in the presence of desferrioxamine, catalase, and Tiron, indicating that hydroxyl radicals are derived from superoxide anions and hydrogen peroxide. In addition, total superoxide dismutase (SOD) activity in the RVLM was decreased in SHRSP compared with WKY. Furthermore, bilateral microinjection of tempol into the RVLM decreased blood pressure in SHRSP but not in WKY, and MnSOD overexpression in the RVLM of SHRSP decreased blood pressure and inhibited sympathetic nerve activity.
  
  
  CONCLUSIONS
  These results suggest that superoxide anions in the RVLM, which generate hydroxyl radicals, are increased in SHRSP and contribute to the neural mechanisms of hypertension in SHRSP.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kishi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hirooka
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Kimura
authors.forename: Koji
authors.initials: K
authors.lastname: Ito
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001923:Brain Chemistry; D002374:Catalase / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D015316:Genetic Therapy; D018698:Glutamic Acid / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D006973:Hypertension / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D015227:Lipid Peroxidation; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism / Q000503:physiopathology*; D009638:Norepinephrine / Q000652:urine; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013113:Spin Labels; D020521:Stroke / Q000235:genetics*; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D013481:Superoxides / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014161:Transduction, Genetic; D014666:Vasomotor System / Q000503:physiopathology
chemical_list: D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D013113:Spin Labels; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D017665:Hydroxyl Radical; D018698:Glutamic Acid; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine; C001803:tempol; D009638:Norepinephrine