Hawkins D J, Meyrick B O, Murray J J
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232.
Biochim Biophys Acta. 1988 May 13;969(3):289-96. doi: 10.1016/0167-4889(88)90064-x.
The aggregation of gel-filtered rabbit platelets by 50 microM ADP was inhibited by a labile factor produced by suspensions of cultured bovine pulmonary artery endothelial cells. Inhibition of aggregation occurred when indomethacin-treated endothelial cells (6.10(5) per ml) and rabbit platelets (3.2.10(8) per ml) were incubated together. This anti-aggregatory activity was characterized as similar to endothelium-derived relaxing factor (EDRF) in that it was unstable at neutral pH and by its inhibition by hemoglobin. The activity was unaffected by treatment of the platelets and endothelial cells with the cyclooxygenase inhibitor, indomethacin, and by the lipoxygenase inhibitor, BW755c. In association with the anti-aggregatory activity, the levels of cyclic GMP were elevated 4-fold. The effect of the EDRF-like product on the levels of cyclic nucleotides was mimicked by treatment of platelets with sodium nitroprusside, an activator of soluble guanylate cyclase; sodium nitroprusside had no measurable effect on the levels of cyclic nucleotides of endothelial cells. We conclude that a factor with the properties of EDRF inhibits platelet aggregation, and that this is associated with an activation of guanylate cyclase as in smooth muscle. Thus, EDRF may exert an inhibitory effect on platelets in a manner analogous to its actions on vascular smooth muscle.
培养的牛肺动脉内皮细胞悬液产生的一种不稳定因子可抑制经凝胶过滤的兔血小板对50微摩尔二磷酸腺苷（ADP）的聚集反应。当将用吲哚美辛处理过的内皮细胞（每毫升6×10⁵个）与兔血小板（每毫升3.2×10⁸个）一起孵育时，聚集反应受到抑制。这种抗聚集活性的特征与内皮源性舒张因子（EDRF）相似，即它在中性pH值下不稳定，且可被血红蛋白抑制。该活性不受用环氧合酶抑制剂吲哚美辛以及脂氧合酶抑制剂BW755c处理血小板和内皮细胞的影响。与抗聚集活性相关的是，环磷酸鸟苷（cGMP）水平升高了4倍。血小板用硝普钠（一种可溶性鸟苷酸环化酶激活剂）处理可模拟EDRF样产物对环核苷酸水平的影响；硝普钠对内皮细胞的环核苷酸水平没有可测量的影响。我们得出结论，一种具有EDRF特性的因子可抑制血小板聚集，并且这与平滑肌中一样的鸟苷酸环化酶激活有关。因此，EDRF可能以类似于其对血管平滑肌作用的方式对血小板发挥抑制作用。
