Hyperuricemia, oxidative stress, and carotid artery tone in experimental renal insufficiency.
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.
Kurra
Venla
V
Medical School, University of Tampere, Tampere, Finland.
Eräranta
Arttu
A
Jolma
Pasi
P
Vehmas
Tuija I
TI
Riutta
Asko
A
Moilanen
Eeva
E
Tahvanainen
Anna
A
Kalliovalkama
Jarkko
J
Niemelä
Onni
O
Myllymäki
Juhani
J
Mustonen
Jukka
J
Pörsti
Ilkka
I
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
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