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 2α (8-iso-PGF 2α ) excretion and plasma total peroxyl radical-trapping capacity (TRAP), respectively. RESULTS Plasma creatinine was elevated twofold in NX rats, but neither NX noroxonic acid diet influenced blood pressure. Urinary 8-iso-PGF 2α 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 urinary8-iso-PGF 2α 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 2α excretion, increased plasma TRAP, and improved NO-mediated vasorelaxation in the carotid artery in experimental renal insufficiency.