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

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.