title: Angiotensin II in paraventricular nucleus contributes to sympathoexcitation in renal ischemia-reperfusion injury by AT1 receptor and oxidative stress.
abstract: BACKGROUND
  To investigate the effect of angiotensin II (Ang II) in the hypothalamic paraventricular nucleus (PVN) on renal ischemia-reperfusion (IR) injury and to assay the role of renal sympathetic nerve activity (RSNA).
  
  
  METHODS
  A cannula was inserted into the right side PVN in Sprague-Dawley rats for microinjection of Ang II (3, 30, and 300 ng); Ang II AT1 receptor antagonist, losartan (0.3 μg); and the superoxide dismutase (SOD) mimetic, tempol (20 nmol) before right side nephrectomy. After 1 wk, renal IR injury was induced by clamping the left renal artery for 45 min, and then reperfusion for 3 or 24 h. The extent of renal damage was determined by evaluation of renal functional indices. RSNA was recorded in all groups. Oxidative stress indices (SOD activity and malondialdehyde levels) were assayed in the PVN.
  
  
  RESULTS
  Microinjection of pharmacologic doses of Ang II into the PVN exaggerated renal IR injury, increased RSNA and oxidative stress in the PVN dose dependently. The effects of Ang II (3 ng) was prevented by pretreatment with losartan into the PVN. Furthermore, the deleterious effects of Ang II on renal IR injury, RSNA, and oxidative stress were abolished by pretreatment with tempol.
  
  
  CONCLUSIONS
  These results indicate that the PVN is a responsive site for central Ang II increment damage in renal ischemia-reperfusion injury. We suggested the central effects of Ang II in the PVN on renal IR injury are mediated by AT1 receptors and oxidative stress in the PVN, and the peripheral effects by a sympathetic pathway.
authors.affiliation: Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: b-seifi@tums.ac.ir.
authors.forename: Behjat
authors.initials: B
authors.lastname: Seifi
authors.affiliation: Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mehri
authors.initials: M
authors.lastname: Kadkhodaee
authors.affiliation: Department of Biostatistics, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Enayatollah
authors.initials: E
authors.lastname: Bakhshi
authors.affiliation: Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mina
authors.initials: M
authors.lastname: Ranjbaran
authors.affiliation: Department of Neurosciences and Addiction, School of Advanced in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Zahmatkesh
authors.affiliation: Department of Physiology and Pharmacology, Medical School, Bushehr University of Medical Sciences, Bushehr, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Sedaghat
authors.affiliation: Department of Physiology, International Campus, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Parisa
authors.initials: P
authors.lastname: Ahghari
authors.affiliation: Research Department, EqlimDanesh Co. Ltd, Tehran, Iran.
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Esmaeili
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000098:blood supply / Q000294:innervation; D007674:Kidney Diseases / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000502:physiology; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D013113:Spin Labels; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
chemical_list: C524087:Agtrap protein, rat; D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D003497:Cyclic N-Oxides; D011945:Receptors, Angiotensin; D013113:Spin Labels; D000804:Angiotensin II; D019808:Losartan; C001803:tempol
keywords: Ang II; Paraventricular nucleus; Renal ischemia–reperfusion; Sympathetic nerve activity