Ritter J M
Br J Pharmacol. 1984 Oct;83(2):409-18. doi: 10.1111/j.1476-5381.1984.tb16501.x.
Synthesis of vascular epoprostenol (PGI2) and platelet thromboxane (TX) A2 is influenced by the coagulation cascade in incompletely understood ways. To elucidate this, prostanoids were determined in human blood anticoagulated by different drugs and incubated with and without rat aortic rings. Control incubations were performed in Hanks balanced salt solution. PGI2 and TXA2 synthesis were assessed by radioimmunoassay of their stable hydrolysis products 6-oxo-prostaglandin (PG) F1 alpha and TXB2. Fresh aortic rings incubated in Hanks solution with a thrombin inhibitor (TCK) synthesized similar quantities of 6-oxo-PGF1 alpha in the presence or absence of sodium citrate. In contrast, the intracellular calcium antagonist TMB-8 inhibited 6-oxo-PGF1 alpha synthesis. In contrast to the finding in Hanks solution, sodium citrate inhibited 6-oxo-PGF1 alpha synthesis by fresh aortic rings incubated in blood anticoagulated with TCK. However, TXB2 synthesis was not affected by citrate. Blood incubated alone at 37 degrees C in plain glass tubes generated a small amount of immunoreactive 6-oxo-PGF1 alpha. A thromboxane synthase inhibitor, OKY1581, increased immunoreactive 6-oxo-PGF1 alpha. However, blood anticoagulated with TCK and incubated similarly, generated no detectable 6-oxo-PGF1 alpha either in the presence or absence of OKY1581, showing that 6-oxo-PGF1 alpha synthesis in the previous experiments was dependent on the vascular rings. OKY1581 had little or no effect on 6-oxo-PGF1 alpha synthesis in incubations of fresh aortic rings with blood anticoagulated with TCK, despite inhibition of TXB2 synthesis. However, OKY1581 increased 6-oxo-PGF1 alpha synthesis by rings pretreated with acetylsalicylic acid (ASA) when incubated in blood, presumably by diversion of platelet endoperoxide to vascular PGI2 synthase. Sodium citrate did not influence the increase in 6-oxo-PGF1 alpha synthesis by ASA pretreated aortic rings caused by OKY1581 in whole blood. This implies that the PGI2 stimulating activity of whole blood in the absence of citrate exerts its effect proximal to PGI2 synthase. It is concluded that a low molecular weight serum factor formed during activation of the intrinsic coagulation pathway in blood, modulates PGI2/TXA2 balance by an action on vascular cyclo-oxygenase, possibly by an effect on intracellular calcium.
血管前列环素（PGI2）和血小板血栓素（TX）A2的合成受凝血级联反应的影响，其方式尚不完全清楚。为阐明这一点，我们测定了用不同药物抗凝并在有或无大鼠主动脉环的情况下孵育的人血中的前列腺素。对照孵育在汉克斯平衡盐溶液中进行。通过对其稳定水解产物6-氧代前列腺素（PG）F1α和TXB2的放射免疫测定来评估PGI2和TXA2的合成。在含有凝血酶抑制剂（TCK）的汉克斯溶液中孵育的新鲜主动脉环，无论有无柠檬酸钠，合成的6-氧代-PGF1α量相似。相比之下，细胞内钙拮抗剂TMB-8抑制了6-氧代-PGF1α的合成。与在汉克斯溶液中的发现相反，柠檬酸钠抑制了在TCK抗凝血液中孵育的新鲜主动脉环的6-氧代-PGF1α合成。然而，TXB2的合成不受柠檬酸盐的影响。在普通玻璃管中于37℃单独孵育的血液产生少量免疫反应性6-氧代-PGF1α。血栓素合酶抑制剂OKY1581增加了免疫反应性6-氧代-PGF1α。然而，用TCK抗凝并类似孵育的血液，无论有无OKY1581，均未检测到6-氧代-PGF1α，这表明先前实验中6-氧代-PGF1α的合成依赖于血管环。尽管抑制了TXB2的合成，但OKY1581对用TCK抗凝血液孵育的新鲜主动脉环中6-氧代-PGF1α的合成几乎没有影响。然而，当在血液中孵育时，OKY1581增加了用乙酰水杨酸（ASA）预处理的环的6-氧代-PGF1α合成，推测是通过将血小板内过氧化物转移至血管PGI2合酶。柠檬酸钠不影响全血中OKY1581引起的ASA预处理主动脉环6-氧代-PGF1α合成的增加。这意味着在无柠檬酸盐情况下全血的PGI2刺激活性在PGI2合酶近端发挥作用。结论是，血液中内源性凝血途径激活过程中形成的一种低分子量血清因子，通过作用于血管环氧化酶，可能通过影响细胞内钙，调节PGI2/TXA2平衡。
