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在酸盐耐受性的发展过程中,血小板释放的氧化和超氧化:补充酸盐的效果

Gary E McVeigh¹, Paul Hamilton, Martin Wilson

¹Department of Therapeutics and Pharmacology, The Queen's University of Belfast, North Ireland, UK. g.mcveigh@qub.ac.uk

|July 10, 2002

概括

持续的酸甘 (NTG) 治疗增加了血小板自由基的产生,有助于耐受性. 与NTG同时使用酸盐 (维生素C) 可以减轻这些影响,这表明抗氧化剂在酸盐治疗中的作用.

科学领域:

心血管药理学心血管药理学
氧化应激和氧化信号

背景情况:

持续的有机酸盐给药导致耐受性,减少治疗效益.
改变的超氧化物产生和氧化 (NO) 的生物可用性与酸盐耐受性有关.
抗氧化剂可能有助于改善酸盐耐受性的发展.

研究的目的:

为了研究连续的透皮甘 (NTG) 对血小板自由基活性的影响.
评估补充酸盐 (维生素C) 对NTG诱导的血小板功能变化和氧化应激的影响.
评估NTG和酸盐对氧化合成酶 (NOS) 活性,NAD,P) H氧化酶活性和循环氨酸单酸盐 (cGMP) 水平的影响.

主要方法:

在参与者中连续三天通过皮肤NTG (10毫克/24小时) 给药.
在单独的组中,与NTG同时服用补充性酸盐 (2.4g/24小时) 和NTG.
测量血小板氧化 (NO) 和超氧化 (O2*-) 生产,NAD(P) H氧化酶活性,NOS活性和cGMP含量.
使用放射性动脉压脉冲波形进行血液动力学监测.

主要成果:

持续使用NTG显著增加了血小板NO和O2*-的产生 (P<0.01).
同时,NTG治疗也增加了血小板中的NAD,P) H氧化酶活性和cGMP含量 (P<0.05).
同时使用NTG与甲酸减弱了血小板NO和O2*释放的增加.

结论:

连续通过皮肤输入的NTG会增加血小板NO和O2*-的产生以及NAD(P) H氧化酶的活性.
口服 Askorbate 抑制了这些由 NTG 诱导的氧化变化.
动脉脉冲轮分析发现了尽管预期的耐受性,但仍然存在残留的血液动力学作用.

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