Durand S, Fromy B, Koïtka A, Tartas M, Saumet J L, Abraham P
Laboratoire de Physiologie et Explorations Vasculaires, Centre Hospitalier Universitaire, 49033 Angers Cedex, France.
Br J Pharmacol. 2002 Oct;137(3):384-90. doi: 10.1038/sj.bjp.0704868.
1 Acetyl salicyclic acid (aspirin) irreversibly blocks cyclo-oxygenase (COX). This effect is short-lived in endothelial or smooth muscle cells due to resynthesis but long-lived in platelets devoid of synthesis ability. Aspirin blocks the anodal current-induced vasodilatation, suggesting participation by prostaglandin (PG). We analysed the time course of the effect of aspirin as an indirect indicator of the origin of the PG possibly involved in anodal current-induced vasodilatation. 2 In healthy volunteers, vasodilatation, estimated from the peak cutaneous vascular conductance (CVC(peak)), was recorded in the forearm during and in the 20 min following 5 min, 0.10 mA transcutaneous anodal current application, using deionized water as a vehicle. CVC(peak) was normalized to 44 degrees C heat-induced maximal vasodilatation and expressed in per cent values. Experiments were performed before and at 2 and 10 h, 3, 7, 10 and 14 days after blinded 1-g aspirin or placebo treatment. 3 CVC(peak) (mean+/-s.d.mean) after aspirin vs placebo was 13.6+/-14.5 vs 65.0+/-32.1 (P<0.05) 14.7+/-4.2 vs 87.5+/-31.9 (P<0.05), 18.1+/-10.2 vs 71.6+/-26.8 (P<0.05), 42.5+/-23.4 vs 73.3+/-26.8 (non significant, NS), 60.2+/-24.3 vs 75.2+/-26.9 (NS), 52.1+/-18.5 vs 67.9+/-32.1 (NS) at 2 and 10 h and at days 3, 7, 10 and 14 respectively. 4 Aspirin inhibition of anodal current-induced vasodilatation persists long after endothelial and smooth muscle cyclo-oxygenases are assumed to be restored. This suggests that the PG involved in this response are not endothelial- or smooth muscle-derived. The underlying mechanism of this unexpected long-lived inhibition of vasodilatation by single high dose aspirin remains to be studied.
1 乙酰水杨酸(阿司匹林)不可逆地阻断环氧化酶(COX)。由于重新合成,这种作用在内皮细胞或平滑肌细胞中持续时间较短,但在缺乏合成能力的血小板中持续时间较长。阿司匹林阻断阳极电流诱导的血管舒张,提示前列腺素(PG)参与其中。我们分析了阿司匹林作用的时间进程,以此作为可能参与阳极电流诱导血管舒张的PG来源的间接指标。2 在健康志愿者中,使用去离子水作为载体,在施加5分钟、0.10 mA经皮阳极电流期间及之后20分钟内,记录前臂根据皮肤血管传导峰值(CVC(peak))估算的血管舒张情况。CVC(peak)以44℃热诱导的最大血管舒张为标准进行归一化,并以百分比值表示。在给予1克阿司匹林或安慰剂进行盲法治疗前、治疗后2小时和10小时、3天、7天、10天和14天进行实验。3 阿司匹林组与安慰剂组相比,CVC(peak)(均值±标准差均值)在2小时和10小时以及第3天、7天、10天和14天分别为13.6±14.5对65.0±32.1(P<0.05)、14.7±4.2对87.5±31.9(P<0.05)、18.1±10.2对71.6±26.8(P<0.05)、42.5±23.4对73.3±26.8(无显著性差异,NS)、60.2±24.3对75.2±26.9(NS)、52.1±18.5对67.9±32.1(NS)。4 阿司匹林对阳极电流诱导血管舒张的抑制作用在内皮和平滑肌环氧化酶被认为恢复后仍持续很长时间。这表明参与该反应的PG并非内皮或平滑肌来源。单次高剂量阿司匹林对血管舒张这种意外的长期抑制作用的潜在机制仍有待研究。