Reilly I A, Roy L, Fitzgerald G A
Br Med J (Clin Res Ed). 1986 Apr 19;292(6527):1037-9. doi: 10.1136/bmj.292.6527.1037.
Thromboxane A2, the predominant cyclo-oxygenase product of arachidonic acid in platelets, is a potent vasoconstrictor and platelet agonist. Analysis of urinary metabolites by gas chromatography and mass spectrometry is a specific non-invasive method of measuring the biosynthesis of thromboxane that avoids the problem of platelet activation ex vivo. Excretion of the major urinary thromboxane metabolite, 2,3-dinor-thromboxane B2, was significantly increased (p less than 0.001) in 10 patients (nine women) with systemic sclerosis complicated by Raynaud's phenomenon compared with healthy controls (486 (SD 88) v 162 (38) ng/g creatinine) and increased further in the patients (to 1007 (212) ng/g creatinine) during application of a cold stimulus sufficient to induce digital vasoconstriction. Consistent with an increase in platelet-vascular interactions in vivo, excretion of a prostacyclin metabolite was also significantly increased (p less than 0.005) in the patients with systemic sclerosis (248 (39) v 112 (10) ng/g creatinine) and tended to increase further on cooling. Biosynthesis of thromboxane is increased in patients with systemic sclerosis and may exacerbate digital vasospasm that such patients develop when cold. This observation and the concomitant increase in the formation of prostacyclin provide a rationale for evaluating compounds that prevent the synthesis of thromboxane A2 or inhibit its action while preserving the potential homoeostatic role of prostacyclin.
血栓素A2是血小板中花生四烯酸主要的环氧化酶产物，是一种强效血管收缩剂和血小板激动剂。通过气相色谱和质谱分析尿代谢产物是一种测量血栓素生物合成的特异性非侵入性方法，可避免体外血小板激活的问题。与健康对照者相比，10例（9例女性）合并雷诺现象的系统性硬化症患者尿中主要血栓素代谢产物2,3-二去甲血栓素B2的排泄量显著增加（p<0.001）（486（标准差88）对162（38）ng/g肌酐），在给予足以诱发指端血管收缩的冷刺激时，患者的排泄量进一步增加（至1007（212）ng/g肌酐）。与体内血小板-血管相互作用增加一致，系统性硬化症患者中前列环素代谢产物的排泄量也显著增加（p<0.005）（248（39）对112（10）ng/g肌酐），且在冷却时往往进一步增加。系统性硬化症患者的血栓素生物合成增加，可能会加重此类患者遇冷时出现的指端血管痉挛。这一观察结果以及同时出现的前列环素生成增加，为评估可预防血栓素A2合成或抑制其作用同时保留前列环素潜在稳态作用的化合物提供了理论依据。
