Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824-1317, USA.
J Pharmacol Exp Ther. 2010 Jun;333(3):758-63. doi: 10.1124/jpet.109.160184. Epub 2010 Mar 9.
Uric acid (UA) results from xanthine oxidase (XO) catabolism of xanthine and is the final product of purine catabolism in humans. In this species, hyperuricemia is associated with gout, nephropathy, and increased cardiovascular disease risk. Although the effects of hyperuricemia in vascular biology are overall controversial, UA has been described as an antioxidant and as potentially improving endothelial function. Hypertension is associated with endothelial dysfunction. We hypothesized that UA improves the endothelial function of aorta from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. UA (100 microM) in the presence of the uricase inhibitor oxonic acid (10 microM) did not modify relaxation to acetylcholine (ACh) (1 nM-10 microM) in the aorta from nontreated, sham normotensive, and DOCA-salt hypertensive rats [response to 10 microM ACh for UA versus vehicle, respectively: nontreated = 37 +/- 7 versus 48 +/- 7%, sham = 53 +/- 15 versus 57 +/- 20%, DOCA = 81 +/- 4 versus 85 +/- 2% from 20 microM prostaglandin 2alpha (PGF(2alpha))-induced contraction]. Allopurinol (100 microM), a XO inhibitor, did not significantly alter the ACh-induced relaxation of sham and DOCA aortic rings (response to 10 microM ACh for allopurinol versus vehicle, respectively: sham = 61 +/- 5 versus 68 +/- 9%, DOCA = 87 +/- 6 versus 88 +/- 3% from 20 microM PGF(2alpha)-induced contraction). Uricemia, ranging from unmeasurable to 547 microM in sham and to 506 microM in DOCA rats, was not significantly different between these two groups. The expression and activity of XO, as well as the expression of uricase, were not different between sham and DOCA rat aorta. We conclude that, at least in vitro, UA does not affect the ACh-induced relaxation of normotensive and DOCA-salt hypertensive rats.
尿酸（UA）是黄嘌呤氧化酶（XO）分解黄嘌呤的产物，是人类嘌呤分解代谢的终产物。在这种物种中，高尿酸血症与痛风、肾病和心血管疾病风险增加有关。尽管高尿酸血症对血管生物学的影响总体上存在争议，但 UA 已被描述为一种抗氧化剂，并可能改善内皮功能。高血压与内皮功能障碍有关。我们假设 UA 可改善去氧皮质酮醋酸盐（DOCA）-盐性高血压大鼠主动脉的内皮功能。在尿酸酶抑制剂氧嗪酸（10 microM）存在的情况下，UA（100 microM）并未改变未处理的、假手术正常血压和 DOCA-盐性高血压大鼠主动脉对乙酰胆碱（ACh）（1 nM-10 microM）的舒张反应[分别为 UA 与载体的 10 microM ACh 反应：未处理 = 37 +/- 7 对 48 +/- 7%，假手术 = 53 +/- 15 对 57 +/- 20%，DOCA = 81 +/- 4 对 85 +/- 2%，来自 20 microM 前列腺素 2alpha（PGF(2alpha)）诱导的收缩]。XO 抑制剂别嘌呤醇（100 microM）并未显著改变 sham 和 DOCA 主动脉环对 ACh 诱导的舒张反应（别嘌呤醇与载体的 10 microM ACh 反应分别为： sham = 61 +/- 5 对 68 +/- 9%，DOCA = 87 +/- 6 对 88 +/- 3%，来自 20 microM PGF(2alpha)诱导的收缩）。 sham 和 DOCA 大鼠的血尿酸范围从无法测量到 547 microM 到 506 microM，两组之间没有显著差异。 sham 和 DOCA 大鼠主动脉的 XO 表达和活性以及尿酸酶的表达没有差异。我们得出结论，至少在体外，UA 不会影响正常血压和 DOCA-盐性高血压大鼠的 ACh 诱导舒张。
