title: Losartan reduces oxidative stress within the rostral ventrolateral medulla of rats with renovascular hypertension.
abstract: BACKGROUND
  Previous studies showed that the microinjection of antioxidants or the overexpression of superoxide dismutase within the rostral ventrolateral medulla (RVLM) reduces hypertension and sympathoexcitation in the 2-kidney, 1-clip (2K-1C) model. In this study, we hypothesized that angiotensin II (ANG II) type 1 receptor (AT1R) is involved in the oxidative stress within the RVLM and contributes to cardiovascular dysfunction in renovascular hypertension.
  
  
  METHODS
  Losartan (30mg/kg/day, oral gavage) was administered for 7 consecutive days by week 5 after implantation of the clip (gap width = 0.2mm). Mean arterial pressure, baroreflex, and renal sympathetic nerve activity (rSNA) were evaluated. Superoxide production was evaluated by dihydroethidium (DHE) staining within the RVLM and within a control area. Systemic oxidative stress was characterized by measurement of thiobarbituric acid reactive substances (TBARS) and total glutathione (tGSH) in the blood.
  
  
  RESULTS
  AT1R blockade significantly (P < 0.05) reduced hypertension by approximately 20% (n = 11) and sympathoexcitation to the kidneys by approximately 41% (n = 6) in the 2K-1C rats. Losartan treatment increased the baroreflex sensitivity of rSNA to pressor (67%) and depressor (140%) stimuli in the 2K-1C rats. AT1R blockade caused a significant (66%) reduction in DHE staining within the RVLM but not within the control area, reduced plasma TBARS (from 1.6±0.1 to 1.0±0.1 nmol/ml), and increased tGSH (from 3.4±0.4 to 5.2±0.3 μmol/g Hb) in the 2K-1C group only.
  
  
  CONCLUSIONS
  Our findings suggest that the beneficial effects of ANG II blockade in renovascular hypertension are partly due to preferential reduction of oxidative stress in the RVLM.
authors.affiliation: Cardiovascular Division, Department of Physiology, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Erika E
authors.initials: EE
authors.lastname: Nishi
authors.forename: Cássia T
authors.initials: CT
authors.lastname: Bergamaschi
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Oliveira-Sales
authors.forename: Karin A
authors.initials: KA
authors.lastname: Simon
authors.forename: Ruy R
authors.initials: RR
authors.lastname: Campos
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D017704:Baroreflex / Q000502:physiology; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016896:Treatment Outcome; D020651:Ventral Thalamic Nuclei / Q000187:drug effects / Q000201:enzymology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D017392:Thiobarbituric Acid Reactive Substances; D013482:Superoxide Dismutase; D019808:Losartan
keywords: AT-1 receptor; RVLM.; angiotensin; blood pressure; hypertension; oxidative stress