title: Hyperuricemia, oxidative stress, and carotid artery tone in experimental renal insufficiency.
abstract: BACKGROUND
  Hyperuricemia may play a role in the pathogenesis of cardiovascular disease, but uric acid is also a significant antioxidant. We investigated the effects of oxonic acid-induced hyperuricemia on carotid artery tone in experimental renal insufficiency.
  
  
  METHODS
  Three weeks after 5/6 nephrectomy (NX) or Sham operation, male Sprague-Dawley rats were allocated to 2.0% oxonic acid or control diet for 9 weeks. Blood pressure was monitored using tail cuff, isolated arterial rings were examined using myographs, and blood and urine samples were taken, as appropriate. Oxidative stress and antioxidant status were evaluated by measuring urinary 8-isoprostaglandin F(2 alpha) (8-iso-PGF(2 alpha)) excretion and plasma total peroxyl radical-trapping capacity (TRAP), respectively.
  
  
  RESULTS
  Plasma creatinine was elevated twofold in NX rats, but neither NX nor oxonic acid diet influenced blood pressure. Urinary 8-iso-PGF(2 alpha) excretion was increased over 2.5-fold in NX rats on control diet. Oxonic acid diet increased plasma uric acid 2-3-fold, TRAP 1.5-fold, and reduced urinary 8-iso-PGF(2 alpha) excretion by 60-90%. Carotid vasorelaxation to acetylcholine in vitro, which could be abolished by nitric oxide (NO) synthase inhibition, was reduced following NX, whereas maximal response to acetylcholine was augmented in hyperuricemic NX rats. Vasorelaxation to nitroprusside was impaired in NX rats, whereas oxonic acid diet increased sensitivity also to nitroprusside in NX rats.
  
  
  CONCLUSIONS
  Oxonic acid-induced hyperuricemia reduced oxidative stress in vivo, as evaluated using urinary 8-iso-PGF(2 alpha) excretion, increased plasma TRAP, and improved NO-mediated vasorelaxation in the carotid artery in experimental renal insufficiency.
authors.affiliation: Medical School, University of Tampere, Tampere, Finland.
authors.forename: Venla
authors.initials: V
authors.lastname: Kurra
authors.forename: Arttu
authors.initials: A
authors.lastname: Eräranta
authors.forename: Pasi
authors.initials: P
authors.lastname: Jolma
authors.forename: Tuija I
authors.initials: TI
authors.lastname: Vehmas
authors.forename: Asko
authors.initials: A
authors.lastname: Riutta
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
authors.forename: Anna
authors.initials: A
authors.lastname: Tahvanainen
authors.forename: Jarkko
authors.initials: J
authors.lastname: Kalliovalkama
authors.forename: Onni
authors.initials: O
authors.lastname: Niemelä
authors.forename: Juhani
authors.initials: J
authors.lastname: Myllymäki
authors.forename: Jukka
authors.initials: J
authors.lastname: Mustonen
authors.forename: Ilkka
authors.initials: I
authors.lastname: Pörsti
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D003404:Creatinine / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D033461:Hyperuricemia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009392:Nephrectomy; D018384:Oxidative Stress / Q000187:drug effects*; D010094:Oxonic Acid; D010545:Peroxides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000503:physiopathology*; D014527:Uric Acid / Q000097:blood; D014664:Vasodilation / Q000187:drug effects
chemical_list: D010545:Peroxides; D014527:Uric Acid; C075750:8-epi-prostaglandin F2alpha; C049375:perhydroxyl radical; D010094:Oxonic Acid; D003404:Creatinine; D015237:Dinoprost; D019331:NG-Nitroarginine Methyl Ester