title: Effects of oxonic acid-induced hyperuricemia on mesenteric artery tone and cardiac load in experimental renal insufficiency.
abstract: BACKGROUND
  Recent studies suggest a causal role for increased plasma uric acid in the progression of chronic renal insufficiency (CRI). However, uric acid also functions as an antioxidant with possible beneficial effects.
  
  
  METHODS
  We investigated the influence of hyperuricemia on mesenteric arterial tone (main and second order branch) and morphology in experimental CRI. Forty-four Sprague-Dawley rats were 5/6 nephrectomized (NX) or Sham-operated and fed 2.0% oxonic acid or control diet for 9 weeks.
  
  
  RESULTS
  Oxonic acid feeding elevated plasma uric acid levels 2.4 and 3.6-fold in the NX and Sham groups, respectively. Plasma creatinine and urea were elevated 2-fold and blood pressure increased by 10 mmHg in NX rats, while hyperuricemia did not significantly influence these variables. Right and left ventricular weight, and atrial and B-type natriuretic peptide mRNA content were increased in NX rats, but were not affected by hyperuricemia. In the mesenteric artery, hyperuricemia did not influence vasoconstrictor responses in vitro to norepinephrine or potassium chloride. The small arteries of NX rats featured hypertrophic remodeling independent of uric acid levels: wall to lumen ratio, wall thickness and cross-sectional area were increased without changes in lumen diameter. In the main branch, vasorelaxations to acetylcholine were impaired in NX rats, but were not affected by hyperuricemia. In contrast, relaxations to the large-conductance Ca(2+)-activated K(+)-channel (BKCa) opener NS-1619 were reduced by oxonic acid feeding, whereas responses to nitroprusside were not affected.
  
  
  CONCLUSIONS
  Experimental hyperuricemia did not influence cardiac load or vascular remodeling, but impaired BKCa -mediated vasorelaxation in experimental CRI.
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Tampere, FIN-33014, Tampere, Finland. venla.kurra@gmail.com.
authors.forename: Venla
authors.initials: V
authors.lastname: Kurra
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Tampere, FIN-33014, Tampere, Finland. tuija.vehmas@tampere.fi.
authors.forename: Tuija
authors.initials: T
authors.lastname: Vehmas
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Tampere, FIN-33014, Tampere, Finland. arttu.eraranta@uta.fi.
authors.forename: Arttu
authors.initials: A
authors.lastname: Eräranta
authors.affiliation: Department of Hand Surgery, Tampere University Hospital, Tampere, Finland. jarkko.jokihaara@pshp.fi.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Jokihaara
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Tampere, FIN-33014, Tampere, Finland. paivi.pirttiniemi@pshp.fi.
authors.forename: Päivi
authors.initials: P
authors.lastname: Pirttiniemi
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, Oulu, Finland. heikki.ruskoaho@helsinki.fi.|Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. heikki.ruskoaho@helsinki.fi.
authors.forename: Heikki
authors.initials: H
authors.lastname: Ruskoaho
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, Oulu, Finland. heikki.tokola@oulu.fi.|Department of Pathology, Oulu University Hospital, Oulu, Finland. heikki.tokola@oulu.fi.
authors.forename: Heikki
authors.initials: H
authors.lastname: Tokola
authors.affiliation: Department of Clinical Chemistry, Seinäjoki Central Hospital Laboratory, Seinäjoki, Finland. onni.niemela@epshp.fi.
authors.forename: Onni
authors.initials: O
authors.lastname: Niemelä
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Tampere, FIN-33014, Tampere, Finland. jukka.mustonen@uta.fi.|Department of Internal Medicine, Tampere University Hospital, Tampere, Finland. jukka.mustonen@uta.fi.
authors.forename: Jukka
authors.initials: J
authors.lastname: Mustonen
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Tampere, FIN-33014, Tampere, Finland. ilkka.porsti@uta.fi.|Department of Internal Medicine, Tampere University Hospital, Tampere, Finland. ilkka.porsti@uta.fi.
authors.forename: Ilkka
authors.initials: I
authors.lastname: Pörsti
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D033461:Hyperuricemia / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009392:Nephrectomy; D010094:Oxonic Acid / Q000378:metabolism / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000503:physiopathology; D014527:Uric Acid / Q000097:blood*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D014527:Uric Acid; D010094:Oxonic Acid