Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
Department of Premier Preventive Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
Sci Rep. 2020 Mar 10;10(1):4437. doi: 10.1038/s41598-020-61463-8.
Xanthine oxidoreductase (XOR) inhibitor administration reduces uric acid and reactive oxygen species (ROS) production, and also lowers blood pressure (BP). However, the associations of plasma XOR activity, uric acid level, and oxidative stress levels with BP remain unclear. This cross-sectional study included 156 subjects (68 males, 88 females) registered in the MedCity21 health examination registry without anti-hypertensive or anti-hyperuricemic agent administration. Plasma XOR activity was measured using our highly sensitive novel assay, which is unaffected by uric acid in the sample. BP was also determined, and serum uric acid and derivative of reactive oxygen metabolites (d-ROMs) levels were simultaneously measured. Median plasma XOR activity, serum uric acid, d-ROMs, and mean arterial pressure (MAP) values were 25.7 pmol/h/mL, 5.4 mg/dL, 305 Carr U, and 89.0 mmHg, respectively. Multiple regression analysis showed that plasma XOR activity (β = 0.211, p = 0.019), but not serum uric acid (β = 0.072, p = 0.502), was significantly associated with MAP. In subjects with lower but not higher d-ROMs level, an independent association of plasma XOR activity with MAP was observed (β = 0.428, p = 0.001 and β = 0.019, p = 0.891, respectively; p for interaction = 0.046). XOR may contribute to the pathophysiology of higher BP through ROS but not uric acid production, especially in patients with lower oxidative stress.
黄嘌呤氧化还原酶（XOR）抑制剂的给药可减少尿酸和活性氧（ROS）的产生，还可降低血压（BP）。然而，血浆 XOR 活性、尿酸水平和氧化应激水平与 BP 的相关性尚不清楚。这项横断面研究纳入了 MedCity21 健康检查登记处的 156 名受试者（68 名男性，88 名女性），这些受试者均未接受抗高血压或抗高尿酸血症药物治疗。使用我们高度敏感的新型测定法测定血浆 XOR 活性，该测定法不受样本中尿酸的影响。还测定了 BP，并同时测定了血清尿酸和活性氧代谢物的衍生（d-ROMs）水平。中位数血浆 XOR 活性、血清尿酸、d-ROMs 和平均动脉压（MAP）值分别为 25.7 pmol/h/mL、5.4mg/dL、305 Carr U 和 89.0mmHg。多元回归分析显示，血浆 XOR 活性（β=0.211，p=0.019），而不是血清尿酸（β=0.072，p=0.502），与 MAP 显著相关。在 d-ROMs 水平较低而非较高的受试者中，血浆 XOR 活性与 MAP 呈独立相关（β=0.428，p=0.001 和 β=0.019，p=0.891；p 交互=0.046）。XOR 可能通过 ROS 而不是尿酸生成对较高 BP 的病理生理学产生影响，尤其是在氧化应激水平较低的患者中。
