title: Superoxide anions involved in sympathoexcitation and pressor effects of salusin-β in paraventricular nucleus in hypertensive rats.
abstract: OBJECTIVE
  Salusin-β in paraventricular nucleus (PVN) increases renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), heart rate (HR) and arginine vasopressin (AVP) release in hypertensive rats but not in normal rats. The present study was designed to investigate the downstream molecular mechanism of salusin-β in the PVN in hypertension.
  
  
  METHODS
  Renovascular hypertension was induced by two-kidney, one-clip (2K1C) in male SD rats. Acute experiments were carried out 4 weeks after 2K1C or sham operation under anaesthesia.
  
  
  RESULTS
  MrgA1 mRNA expression and salusin-β level in the PVN as well as plasma salusin-β level were increased in 2K1C rats. Bilateral PVN microinjection of salusin-β increased the RSNA, MAP and HR in 2K1C rats, which were abolished by the pre-treatment with polyethylene glycol-superoxide dismutase (PEG-SOD), the superoxide anion scavenger tempol, the NAD(P)H oxidase inhibitor apocynin or the protein kinase C (PKC) inhibitor chelerythrine chloride (CLC), but not affected by the AT1 receptor antagonist losartan, the Mas receptor antagonist A-779, the NOS inhibitor L-NAME or the GABAA and GABAB receptor antagonists gabazine+CGP-35348. Salusin-β-induced increases in superoxide anion level and NAD(P)H oxidase activity in the PVN were abolished by the PVN pre-treatment with CLC. Salusin-β increased AVP levels in rostral ventrolateral medulla and plasma, which were prevented by the pre-treatment with PEG-SOD, apocynin or CLC in 2K1C rats. Salusin-β augmented the enhanced activity of PKC in the PVN in 2K1C rats.
  
  
  CONCLUSIONS
  Protein kinase C-NAD(P)H oxidase-superoxide anions pathway in the PVN is involved in salusin-β-induced sympathetic activation, pressor response and AVP release in renovascular hypertension.
authors.affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, China.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Sun
authors.forename: L-L
authors.initials: LL
authors.lastname: Zhang
authors.forename: Z-D
authors.initials: ZD
authors.lastname: Fan
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: X-Y
authors.initials: XY
authors.lastname: Gao
authors.forename: Y-M
authors.initials: YM
authors.lastname: Kang
authors.forename: G-Q
authors.initials: GQ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000378:metabolism* / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013481:Superoxides / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C528274:salusin-beta, rat; D013481:Superoxides
keywords: hypertension; salusin; superoxide anions; sympathetic nerve activity; vasopressin