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Prostanoid synthesis by aortic rings in human blood: selective increase of prostacyclin mediated by a serum factor
Author(s) -
Ritter J.M.
Publication year - 1984
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1984.tb16501.x
Subject(s) - prostacyclin , thromboxane a2 , prostaglandin , alpha (finance) , thromboxane b2 , thromboxane , medicine , prostanoid , endocrinology , radioimmunoassay , chemistry , platelet , surgery , construct validity , patient satisfaction
1 Synthesis of vascular epoprostenol (PGI 2 ) and platelet thromboxane (TX) A 2 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. PGI 2 and TXA 2 synthesis were assessed by radioimmunoassay of their stable hydrolysis products 6‐oxo‐prostaglandin (PG) F 1α and TXB 2 . 2 Fresh aortic rings incubated in Hanks solution with a thrombin inhibitor (TCK) synthesized similar quantities of 6‐oxo‐PGF 1α in the presence or absence of sodium citrate. In contrast, the intracellular calcium antagonist TMB‐8 inhibited 6‐oxo‐PGF 1α synthesis. 3 In contrast to the finding in Hanks solution, sodium citrate inhibited 6‐oxo‐PGF 1α synthesis by fresh aortic rings incubated in blood anticoagulated with TCK. However, TXB 2 synthesis was not affected by citrate. 4 Blood incubated alone at 37°C in plain glass tubes generated a small amount of immunoreactive 6‐oxo‐PGF 1α . A thromboxane synthase inhibitor, OKY1581, increased immunoreactive 6‐oxo‐PGF 1α . However, blood anticoagulated with TCK and incubated similarly, generated no detectable 6‐oxo‐PGF 1α either in the presence or absence of OKY1581, showing that 6‐oxo‐PGF 1α synthesis in the previous experiments was dependent on the vascular rings. 5 OKY1581 had little or no effect on 6‐oxo‐PGF 1α synthesis in incubations of fresh aortic rings with blood anticoagulated with TCK, despite inhibition of TXB 2 synthesis. However, OKY1581 increased 6‐oxo‐PGF 1α synthesis by rings pretreated with acetylsalicylic acid (ASA) when incubated in blood, presumably by diversion of platelet endoperoxide to vascular PGI 2 synthase. 6 Sodium citrate did not influence the increase in 6‐oxo‐PGF 1α synthesis by ASA pretreated aortic rings caused by OKY1581 in whole blood. This implies that the PGI 2 stimulating activity of whole blood in the absence of citrate exerts its effect proximal to PGI 2 synthase. 7 It is concluded that a low molecular weight serum factor formed during activation of the intrinsic coagulation pathway in blood, modulates PGI 2 /TXA 2 balance by an action on vascular cyclooxygenase, possibly by an effect on intracellular calcium.