高剂量的阿洛普林醇通过极大减少血管氧化应激而不是通过降低尿酸来改善内皮功能
Jacob George1, Elaine Carr, Justine Davies
1Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
Circulation
|November 30, 2006
概括
阿洛普林醇通过减少血管氧化应激,显著改善心力衰竭患者的内皮功能,观察到急剧的剂量反应关系. 这种益处与抗氧化作用有关,而不是尿酸减少.
科学领域:
- 心脏病学 心脏病学
- 药理学 药理学是指药理学的学科.
- 血管生物学 血管生物学
背景情况:
- 在慢性心力衰竭患者中,阿洛普林醇显示出增强内皮功能的潜力.
- 了解精确的机制和剂量反应对于优化治疗至关重要.
研究的目的:
- 阐明阿洛普林醇对内皮功能作用的机制.
- 建立对心力衰竭中阿洛普林醇效应的剂量反应曲线.
主要方法:
- 在心力衰竭患者中进行了两项随机,安慰剂控制,双盲,交叉研究 (NYHA II-III类).
- 患者接受了阿洛普醇 (300毫克或600毫克) 或安慰剂;第二项研究评估了probenecid (1000毫克) 与安慰剂.
- 用前臂静脉闭塞复合体图测量了内皮功能.
主要成果:
- 与300毫克和安慰剂相比,Allopurinol每天600毫克显著改善了前臂对乙胆的血流反应.
- 酸盐降低剂Pobenecid没有影响内皮功能.
- 高剂量的阿洛普林醇 (600毫克/天) 消除了维生素C敏感的氧化应激.
结论:
- 对于氨醇对内皮功能的积极影响,存在着急剧的剂量反应关系.
- 二醇改善内皮功能主要通过减少血管氧化应激,独立于尿酸减少.
- 阿洛普林醇的抗氧化作用很强,可以显著减轻心力衰竭中的氧化应激.
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