腺苷5′-二磷酸诱导的尿毒症血小板聚集对新型一氧化氮供体GEA 3175的抑制有抵抗力,但对s -亚硝基-n -乙酰青霉胺的抑制没有抵抗力。

Haemostasis Pub Date : 1998-09-01 DOI:10.1159/000022441
P A Whiss, R Larsson
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引用次数: 4

摘要

出血和血栓形成是定期血液透析患者尿毒症的并发症。血管扩张剂和血小板抑制剂一氧化氮(NO)的过量内源性形成被认为是导致出血缺陷的原因。由于暴露于一氧化氮的药物供体,即硝基血管扩张剂,可引起对一氧化氮的耐受性,我们研究了定期血液透析的尿毒症患者的血小板是否受到一氧化氮供体与健康受试者血小板的不同影响。常用的s -亚硝基噻吩s -亚硝基-n -乙酰青霉胺(SNAP)与最近合成的中离子奥唑唑衍生物GEA 3175在体外对腺苷5'-二磷酸(ADP)诱导的血小板聚集的抑制能力进行了比较。发现尿毒症患者一氧化氮生成的最终产物亚硝酸盐+硝酸盐显著增加。SNAP抑制血小板聚集的能力在两组之间仅略有差异。然而,与对照组相比,GEA 3175对尿毒症血小板聚集的抑制能力显著降低。促红细胞生成素(EPO)与NO的相互作用已有较早的报道。体外健康供体血小板中添加EPO对NO供体抑制血小板聚集能力无显著影响,但有增强SNAP作用的趋势,而GEA 3175的作用被抑制。这些结果提示在尿毒症血小板活化中对NO供体的化合物特异性抵抗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Adenosine 5'-diphosphate-induced platelet aggregation in uremia shows resistance to inhibition by the novel nitric oxide donor GEA 3175 but not by S-nitroso-N-acetylpenicillamine.

Both bleeding and thrombosis are complications of uremia in patients on regular hemodialysis. An excessive endogenous formation of the vasodilator and platelet inhibitor nitric oxide (NO) has been proposed to contribute to the bleeding defect. Since exposure to pharmacological donors of NO, nitrovasodilators, can cause tolerance to NO, we investigated whether platelets from uremic patients on regular hemodialysis are influenced differently by NO donors than platelets from healthy subjects. A frequently used S-nitrosothiol, S-nitroso-N-acetylpenicillamine (SNAP), was compared to a recently synthezised mesoionic oxatriazole derivate, GEA 3175, regarding its capacity to inhibit adenosine 5'-diphosphate (ADP)-induced platelet aggregation in vitro. The final products of NO production, nitrite + nitrate, were found to be significantly increased in uremic patients. The capacity to inhibit platelet aggregation by SNAP was only slightly different between the groups. However, GEA 3175 showed a significantly marked and reduced capacity to inhibit aggregation of uremic platelets compared to controls. Interactions of erythropoietin (EPO) with NO have earlier been reported. Addition of EPO to platelets from healthy donors in vitro did not significantly influence the NO donor capacity to inhibit platelet aggregation, but showed a tendency to enhance the effect of SNAP while the effect of GEA 3175 was inhibited. These results suggest compound-specific resistance to NO donors in uremic platelet activation.

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