Weber A A, Neuhaus T, Seul C, Düsing R, Schrör K, Sachinidis A, Vetter H
Medizinische Poliklinik, Universität Bonn, Germany.
Eur J Pharmacol. 1996 Aug 8;309(2):209-13. doi: 10.1016/0014-2999(96)00338-x.
The present study investigated the metabolism of glyceryl trinitrate by washed human platelets as compared to that by rat vascular smooth muscle cells. Possible changes in metabolism after induction of nitrate tolerance were also studied in both systems. Incubation of the cells with glyceryl trinitrate (0.1 mM) resulted in a time-dependent release of nitrite (NO2-) amounting to 6.30 +/- 0.63 nmol mg protein-1 h-1 in vascular smooth muscle cells and 0.61 +/- 0.08 nmol mg protein-1 h-1 for platelets, respectively. The nitric oxide (NO) scavenger, oxyhemoglobin (10 microM), significantly reduced NO2- generation in both cell types studied. Nitrate tolerance was induced by incubation of the cells with glyceryl trinitrate (2 mM) for 2 h. In tolerant vascular smooth muscle cells as well as in tolerant platelets, NO2- release was significantly reduced. The inhibitory capacity of glyceryl trinitrate on ADP (6 microM)-induced platelet aggregation and on intracellular Ca2+ signals was significantly reduced in tolerant platelets. The data show a direct metabolism of glyceryl trinitrate by human blood platelets which is subject to a type of tolerance development similar to that in vascular smooth muscle cells.
本研究调查了与大鼠血管平滑肌细胞相比，经洗涤的人血小板对硝酸甘油的代谢情况。还研究了在这两种体系中诱导产生硝酸盐耐受性后代谢可能发生的变化。用硝酸甘油（0.1 mM）孵育细胞，结果在血管平滑肌细胞中，亚硝酸盐（NO₂⁻）呈时间依赖性释放，释放量为6.30±0.63 nmol mg蛋白⁻¹ h⁻¹，在血小板中为0.61±0.08 nmol mg蛋白⁻¹ h⁻¹。一氧化氮（NO）清除剂氧合血红蛋白（10 μM）显著降低了所研究的两种细胞类型中NO₂⁻的生成。通过用硝酸甘油（2 mM）孵育细胞2小时来诱导产生硝酸盐耐受性。在产生耐受性的血管平滑肌细胞以及产生耐受性的血小板中，NO₂⁻释放均显著减少。在产生耐受性的血小板中，硝酸甘油对ADP（6 μM）诱导的血小板聚集和细胞内Ca²⁺信号的抑制能力显著降低。数据表明人血小板可直接代谢硝酸甘油，且这种代谢会产生一种类似于血管平滑肌细胞中的耐受性。
