Uric Acid and Hypertension in African-Americans

非裔美国人的尿酸和高血压

• 批准号: 7413657
• 负责人: MARK S. SEGAL
• 金额: $ 67.16万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7413657
• 关键词: Acids; Adverse effects; African American; Albuminuria; Allopurinol; Animal Model; Animals; Blood Pressure; Blood Vessels; C-reactive protein; CCL2 gene; Cardiac; Cardiovascular system; Chemotactic Factors; Chlorthalidone; Clinic; Clinical Data; Clinical Research; Clinical Trials; Condition; Cultured Cells; Data; Development; Diuretics; Dose; Double-Blind Method; End Point; Endothelium; Enrollment; Epidemiologic Studies; Event; Frequencies; Functional disorder; Glomerular Filtration Rate; Goals; Gout; Growth; Hour; Human; Hyperinsulinism; Hyperlipidemia; Hypertension; Hypertriglyceridemia; Hyperuricemia; Hypokalemia; Hypotension; Impairment; Incidence; Inflammation; Insulin Resistance; International; Iothalamate; Isoprostanes; Kidney; Leukocytes; Life Style; Link; Malondialdehyde; Measures; Mediator of activation protein; Messenger RNA; Metabolic; Metabolic syndrome; Microalbuminuria; Micropuncture; Modification; Monitor; NADPH Oxidase; Nitric Oxide; Outcome; Oxidants; Oxidative Stress; Patients; Pharmacotherapy; Placebo Control; Placebos; Plasma; Population; Prevention; Production; Proteins; Randomized; Range; Rattus; Renal Blood Flow; Renal Plasma Flow; Research Personnel; Risk; Serum; Side; Societies; Sodium; Sodium-Restricted Diet; Staging; Stress; Testing; Therapeutic; Therapeutic Agents; Thiazide Diuretics; Time; Treatment Protocols; Upper arm; Uric Acid; Vascular Endothelial Cell; Week; Xanthine Oxidase; base; blood pressure regulation; brachial artery; day; glomerulosclerosis; hemodynamics; impaired glucose tolerance; improved; pressure; prevent; programs; protein expression; research study; thiazide; urinary; vasoconstriction; xanthine oxidase inhibitor; young adult

DESCRIPTION (provided by applicant): Thiazide diuretics are associated with many metabolic side effects including hyperuricemia, gout, insulin resistance, and hyperlipidemia. These very conditions are already highly prevalent in African-Americans. We and others have generated a large body of epidemiologic, animal model, cell culture, and preliminary data in patients that suggests that uric acid is itself a mediator of hypertension, endotheliai dysfunction, and systemic inflammation. In our animal models elevated uric acid leads to increased blood pressure (BP) and lowering uric acid decreases BP. Furthermore, our study of hypertensive young adults suggests that allopurinol treatment leads to a decrease in uric acid associated with a lower BP. Our hypothesis is that thiazide-induced hyperuricemia decreases the efficacy of thiazides in controlling BP, leads to endothelial dysfunction, and increases the incidence of insulin resistance and impaired glucose tolerance. This hypothesis will be tested in a randomized double-blind placebo-controlled 2x2 factorial clinical trial of 8- week duration in which a total of 300 African-Americans patients with stage 1 hypertension (BP: 140-159/90- 99 mm Hg) will be assigned to one of four regimens: 1) a thiazide-like diuretic, chlorthalidone 25 mg/day, and a xanthine oxidase inhibitor, allopurinol; 2) chlorthalidone 25 mg/day and placebo; 3) placebo or 4) allopurinol. All subjects will receive a low-sodium diet. Our hypothesis predicts that lowering uric acid will enhance BP control, prevent endothelial dysfunction, reduce systemic inflammation, improve g.ucose tolerance and reduce hyperinsulinemia. In Aim 1 we test the hypothesis that prevention of chlorthalidone - induced hyperuricemia with allopurinol results in improved BP control. In Aim 2 we test the hypothesis that prevention of chlorthalidone-induced increase in serum uric acid by allopurinol improves endothelial function and reduces systemic inflammation. In Aim 3 we test the hypothesis that prevention of chlorthalidone induced hyperuricemia with allopurinol improves renal blood flow and GFR and prevents microalbumineria.

描述（由申请人提供）：噻嗪类利尿剂与许多代谢副作用相关，包括高尿酸血症、痛风、胰岛素抵抗和高脂血症。这些情况在非裔美国人中已经非常普遍。我们和其他人已经获得了大量的流行病学、动物模型、细胞培养和患者初步数据，表明尿酸本身就是高血压、内皮功能障碍和全身炎症的介质。在我们的动物模型中，尿酸升高会导致血压 (BP) 升高，而尿酸降低则会降低血压。此外，我们对高血压年轻人的研究表明，别嘌呤醇治疗可导致尿酸降低，从而降低血压。我们的假设是，噻嗪类药物引起的高尿酸血症会降低噻嗪类药物控制血压的功效，导致内皮功能障碍，并增加胰岛素抵抗和糖耐量受损的发生率。这一假设将在一项为期 8 周的随机双盲安慰剂对照 2x2 析因临床试验中得到检验，该试验总共有 300 名患有 1 期高血压（血压：140-159/90-99 mm Hg）的非裔美国人患者将被分配到四种方案之一：1) 噻嗪类利尿剂、氯噻酮 25 毫克/天和黄嘌呤氧化酶抑制剂，别嘌呤醇； 2) 氯噻酮 25 mg/天和安慰剂； 3) 安慰剂或 4) 别嘌呤醇。所有受试者都将接受低钠饮食。我们的假设预测，降低尿酸将增强血压控制，预防内皮功能障碍，减少全身炎症，改善葡萄糖耐受性并减少高胰岛素血症。在目标 1 中，我们检验了以下假设：用别嘌呤醇预防氯噻酮诱发的高尿酸血症可改善血压控制。在目标 2 中，我们检验了以下假设：通过别嘌呤醇预防氯噻酮诱导的血清尿酸升高可改善内皮功能并减少全身炎症。在目标 3 中，我们检验了以下假设：用别嘌呤醇预防氯噻酮诱发的高尿酸血症可改善肾血流量和 GFR，并预防微量白蛋白血症。

项目成果

Evaluation of stability and sensitivity of cell fluorescent labels when used for cell migration.

• DOI: 10.1007/s10895-013-1224-8
• 发表时间: 2013-09
• 期刊: JOURNAL OF FLUORESCENCE
• 影响因子: 2.7
• 作者: Beem, Elaine;Segal, Mark S.
• 通讯作者: Segal, Mark S.

The effect of the addition of allopurinol on blood pressure control in African Americans treated with a thiazide-like diuretic.

添加别嘌呤醇对接受噻嗪类利尿剂治疗的非裔美国人血压控制的影响。

• DOI: 10.1016/j.jash.2015.05.009
• 发表时间: 2015
• 期刊: Journal of the American Society of Hypertension : JASH
• 作者: Segal,MarkS;Srinivas,TitteR;Mohandas,Rajesh;Shuster,JonathanJ;Wen,Xuerong;Whidden,Elaine;Tantravahi,JogiRaju;Johnson,RichardJ
• 通讯作者: Johnson,RichardJ