Matthews J S, McWilliams P J, Key B J, Keen M
Department of Pharmacology, Medical School, University of Birmingham, Edgbaston, UK.
Biochim Biophys Acta. 1995 Nov 30;1269(3):237-42. doi: 10.1016/0167-4889(95)00125-x.
Pretreatment (18 h) of the bovine aortic endothelial cell line AG4762 to 500 microM sodium nitroprusside (SNP), glyceryl trinitrate (GTN) or 3-morpholino-sydnonimine (SIN-1) significantly inhibited 100 nM bradykinin-stimulated prostacyclin (PGI2) release. SIN-1 produced the greatest reduction (67 +/- 6%), followed by SNP (47 +/- 12%) and GTN (45 +/- 9%). Only SIN-1 and GTN inhibited basal PGI2 release where again the effect of SIN-1 (66 +/- 6%) was greater than that of GTN (31 +/- 15%). There was no effect of SNP on basal PGI2 release. We have demonstrated this inhibition of bradykinin-stimulated PGI2 release is not the result of cell death. In addition, 8-bromo-cyclic GMP, whilst having no effect on basal PGI2 release, demonstrated a small but significant inhibition (15 +/- 6%) of the enhanced response to 100 nM bradykinin. These studies may reflect a mechanism by which the release of vasodilators from endothelial cells is altered during therapy with nitrovasodilators and thus may contribute to the development of tolerance to these drugs.
将牛主动脉内皮细胞系AG4762用500微摩尔的硝普钠（SNP）、硝酸甘油（GTN）或3 - 吗啉代西多明（SIN - 1）预处理18小时，可显著抑制100纳摩尔缓激肽刺激的前列环素（PGI2）释放。SIN - 1的抑制作用最强（67±6%），其次是SNP（47±12%）和GTN（45±9%）。只有SIN - 1和GTN抑制基础PGI2释放，同样SIN - 1的作用（66±6%）大于GTN（31±15%）。SNP对基础PGI2释放无影响。我们已证明这种对缓激肽刺激的PGI2释放的抑制不是细胞死亡的结果。此外，8 - 溴环鸟苷酸虽然对基础PGI2释放无影响，但对100纳摩尔缓激肽增强反应有轻微但显著的抑制作用（15±6%）。这些研究可能反映了一种机制，即在用硝基血管扩张剂治疗期间内皮细胞释放血管扩张剂的方式发生改变，因此可能导致对这些药物产生耐受性。
