Heitzer Thomas, Rudolph Volker, Schwedhelm Edzard, Karstens Manuela, Sydow Karsten, Ortak Michelle, Tschentscher Peter, Meinertz Thomas, Böger Rainer, Baldus Stephan
Universitäres Herzzentrum Hamburg, Universitätsklinikum Hamburg-Eppendorf, Germany.
Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1648-52. doi: 10.1161/01.ATV.0000225288.74170.dc. Epub 2006 May 4.
Platelet stimulation and activation are known not only as prerequisite of clot formation but are increasingly recognized as important contributors to inflammation and vascular injury. The present study in patients with symptomatic coronary disease investigated whether platelet adenosine diphosphate receptor blockade by clopidogrel exerts beneficial effects on endothelial nitric oxide bioavailability, oxidative stress, and/or inflammatory status.
One hundred three consecutive patients with symptomatic coronary disease and long-term aspirin therapy were studied. Endothelium-dependent and -independent vasodilation was determined measuring forearm blood flow (FBF)-responses to acetylcholine with and without N(G)-monomethyl-L-arginin (L-NMMA) and sodium nitroprusside, by using venous occlusion plethysmography. Patients were randomized to receive additional treatment with clopidogrel or placebo. Vascular function tests were repeated after 5 weeks and showed significant improvement of acetylcholine-induced vasodilatation and L-NMMA responses in the clopidogrel-added group (max. FBF from 9.8+/-0.3 to 14.7+/-0.4; L-NMMA-response from 3.7+/-0.1 to 6.8+/-0.3 mL/100 mL/min). In contrast, no significant changes were observed in the placebo group. Sodium nitroprusside-induced vasodilation was not changed in either group. Urinary excretion of 8-iso-prostaglandin F2alpha and plasma levels of hsCRP, sCD40L, and RANTES were reduced in patients on additional treatment with clopidogrel, but not in patients on placebo.
Clopidogrel improves endothelial nitric oxide bioavailability and diminishes biomarkers of oxidant stress and inflammation in patients with symptomatic coronary artery disease, suggesting that beyond inhibition of platelet aggregation, adenosine phosphate receptor blockade may also have promising vasoprotective effects.
血小板刺激和激活不仅是血栓形成的先决条件，而且越来越被认为是炎症和血管损伤的重要促成因素。本项针对有症状冠心病患者的研究，调查了氯吡格雷对血小板二磷酸腺苷受体的阻断是否对内皮型一氧化氮生物利用度、氧化应激和/或炎症状态产生有益影响。
对103例连续的有症状冠心病且长期接受阿司匹林治疗的患者进行了研究。采用静脉阻塞体积描记法，通过测量前臂血流（FBF）对乙酰胆碱（有无N(G)-单甲基-L-精氨酸（L-NMMA））和硝普钠的反应，来测定内皮依赖性和非依赖性血管舒张功能。患者被随机分为接受氯吡格雷或安慰剂的额外治疗组。5周后重复进行血管功能测试，结果显示添加氯吡格雷的组中乙酰胆碱诱导的血管舒张和L-NMMA反应有显著改善（最大FBF从9.8±0.3增加到14.7±0.4；L-NMMA反应从3.7±0.1增加到6.8±0.3 mL/100 mL/min）。相比之下，安慰剂组未观察到显著变化。两组中硝普钠诱导的血管舒张均未改变。接受氯吡格雷额外治疗的患者尿中8-异前列腺素F2α排泄量以及血浆中hsCRP、sCD40L和RANTES水平降低，但接受安慰剂治疗的患者未出现此情况。
氯吡格雷可改善有症状冠状动脉疾病患者的内皮型一氧化氮生物利用度，并减少氧化应激和炎症的生物标志物，这表明除抑制血小板聚集外，磷酸腺苷受体阻断可能也具有有前景的血管保护作用。
