Comparison of inhibitory actions of prostacyclin and a new prostacyclin analogue on the aggregation of human platelet in whole blood

A.R. Saniabadi, J.J.F. Belch, G.D.O. Lowe, J.C. Barbenel, C.D. Forbes

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    Abstract

    Prostacyclin (PGI2), an unstable endogenous prostanoid, is a potent vasodilator and inhibitor of platelet aggregation. The use of exogenous PGI2 as an antithrombotic agent is limited by its chemical instability and lack of dissociation between its vasodilatory and antithrombotic actions. Iloprost (ZK36374) is a recently developed, chemically stable, carbacyclin analogue of PGI2. Preliminary evaluation studies have shown a significant dissociation between vasodilatory and antithrombotic actions of Iloprost. We have compared the effects of PGI2 and Iloprost on platelet aggregation in human whole blood. Platelet aggregation was induced by ADP (4 µM), adrenaline (Adr, 0.4 µM) and arachidonic acid (AA, 0.4 mM). Aggregation was quantified as a fall in the number of single platelets counted using the Clay Adams Ultra Flo 100 whole blood platelet counter. In the absence of any PGI2 or Iloprost, each aggregating agent induced up to an 80% fall in the number of single platelets counted. When blood was pre-incubated with PGI2 (1-6 nM) or Iloprost (1-6 nM), aggregation responses to all three aggregating agents were inhibited in a dose-dependent manner. Iloprost was equipotent to PGI2 against ADP-induced aggregation but was more potent than PGI2 against Adr- and AA-induced aggregation. It is concluded that Iloprost, as a chemically stable PGI2 analogue, may be superior to PGI2 as an antithrombotic agent.

    Original languageEnglish
    Pages (from-to)147-153
    Number of pages7
    JournalHaemostasis
    Volume17
    Issue number3
    Publication statusPublished - 1987

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