Hyperuricemia induces endothelial dysfunction
Hyperuricemia induces endothelial dysfunction
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DOI：
10.1111/j.1523-1755.2005.00273.x
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发表时间：
2005-05-01
影响因子：
19.6
通讯作者：
Johnson, RJ
中科院分区：
文献类型：
--
作者：
Khosla, UM;Zharikov, S;Johnson, RJ
背景高尿酸血症与心血管和肾脏疾病有关，可能是通过产生活性氧（ROS）和随后的内皮功能障碍。黄嘌呤氧化酶的酶促作用是产生ROS和尿酸。研究表明，用别嘌呤醇抑制黄嘌呤氧化酶可以逆转内皮功能障碍。此外，大鼠研究表明，高尿酸血症诱导的高血压和血管疾病至少部分逆转的一氧化氮合酶（NOS）底物，L-精氨酸的补充。因此，我们假设尿酸通过抑制一氧化氮的产生诱导内皮功能障碍。在雄性Sprague-Dawley大鼠中通过灌胃尿酸酶抑制剂氧糖酸诱导高尿酸血症;对照大鼠接受溶媒。将别嘌呤醇置于饮用水中以阻断高尿酸血症。大鼠随机分为4组：（1）对照组，（2）仅别嘌呤醇组，（3）仅氧嗪酸组，（4）氧嗪酸+别嘌呤醇组。在第1天和第7天处死大鼠，并分析其血清中的血清尿酸和亚硝酸盐/硝酸盐浓度。尿酸对牛主动脉内皮细胞产生一氧化氮的影响也被确定。Oxonic acid组在第1天和第7天均出现轻度高尿酸血症（P < 0.05）。别嘌呤醇治疗7 d后可逆转高尿酸血症（P
Background. Hyperuricemia has been linked to cardiovascular and renal diseases, possibly through the generation of reactive oxygen species (ROS) and subsequent endothelial dysfunction. The enzymatic effect of xanthine oxidase is the production of ROS and uric acid. Studies have shown that inhibiting xanthine oxidase with allopurinol can reverse endothelial dysfunction. Furthermore, rat studies have shown that hyperuricemia-induced hypertension and vascular disease is at least partially reversed by the supplementation of the nitric oxide synthase (NOS) substrate, L-arginine. Therefore, we hypothesized that uric acid induces endothelial dysfunction by inhibiting nitric oxide production.Methods. Hyperuricemia was induced in male Sprague-Dawley rats with an uricase inhibitor, oxonic acid, by gavage; control rats received vehicle. Allopurinol was placed in drinking water to block hyperuricemia. Rats were randomly divided into four groups: (1) control, (2) allopurinol only, (3) oxonic acid only, and (4) oxonic acid + allopurinol. Rats were sacrificed at 1 and 7 days, and their serum analyzed for serum uric acid and nitrites/nitrates concentrations. The effect of uric acid on nitric oxide production was also determined in bovine aortic endothelial cells.Results. Oxonic acid induced mild hyperuricemia at both 1 and 7 days (P < 0.05). Allopurinol reversed the hyperuricemia at 7 days (P