title: Prostanoid synthesis by aortic rings in human blood: selective increase of prostacyclin mediated by a serum factor.
abstract: 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.
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology; D002951:Citrates / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D011863:Radioimmunoassay; D051381:Rats; D013929:Thromboxane B2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000096:biosynthesis*
chemical_list: D002951:Citrates; D008689:Methacrylates; D011453:Prostaglandins; D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C031517:2-methyl-3-(4-(3-pyridinylmethyl)phenyl)-2-propenoic acid; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; D001241:Aspirin