Nadph Oxidase Activation By Excess Uric Acid In Vitro

Purpose: Uric acid is considered a major antioxidant thatmay protect against aging and oxidative stress. On the other hand, hyperuricemia induced alterations in oxidative homeostasis are commonly associated with increased risk for cardiovasculardisease and mortality. We hypothesized that acute elevated levels of uric acid induce O 2 − production by the activation of NADPH oxidase. Methods: SD male rats were divided into control(C) and Uric acid (UA) groups. The muscle tissues of left ventricle were incubated in Krebs solution without or with allopurinol, apocynin or tiron, 3mg/dL uric acid was placed in UA group, at 37°Cfor 1 h and bubbled continuously with 20% O 2 −5% CO 2 −75% N 2 . Results: NO‐dependent control of MVO 2 stimulated by bradykinin or carbacholwas attenuated in UA (11.1% vs. 23.3% for BK; 13.2% vs. 20.9% for Cch). However, this was reversed by in the presence of apocynin (to 19.1% for BK; 19.6% for Cch) or tiron (to 20.6% for BK; 18.9% for Cch). It was not completely restored by allopurinol. Western blots of left ventricle showed that there was a significant difference between the two groups in the protein for p47 and nitrotyrosine ( P < 0.01, P < 0.05 respectively), but there was no difference in eNOS, xanthine oxidase, p38 kinase, gp91, p22, SOD1 and SOD2. Conclusions: NADPH Oxidase was stimulated in acute hyperuricemia through the activation of p47. NO was inactivated by an increase in O 2 − production. Supported by HL‐PO1‐43023 grant.