Prostacyclins are only weak antagonists of coronary vasospasm induced by authentic thromboxane A2 and serotonin

The actions of prostacyclin and its synthetic analog iloprost on the release and action of platelet-derived serotonin (5-HT) and thromboxane (TX) A2 were studied in vitro. Washed human platelet suspensions (WPS) (4 X 10(8) platelets/ml) were stimulated with arachidonic acid (AA) (30 mumol/L) and the incubate transferred into an organ bath containing bovine coronary arteries (BCA) in Krebs-Henseleit buffer supplemented with a mixture of blocking agents, including indomethacin. This resulted in a biphasic contraction of the coronary arteries, consisting of first, a TXA2-mediated response and second, a 5-HT-mediated response. The 5-HT-mediated reaction was dose-dependently inhibited by methysergide (IC50: 80 nmol/L). Treatment of the WPS with prostacyclin (PGI2) or iloprost prior to stimulation by AA resulted in a dose-dependent inhibition of the 5-HT-mediated contraction, due to inhibition of 5-HT release. The TXA2-mediated component, as well as the concentration of immunoreactive TXB2 in the bath medium, remained unchanged. Addition of PGI2 or iloprost to the BCA prior to transfer of stimulated WPS to the bath medium was followed by a dose-dependent inhibition of both phases. This, however, required concentrations of 100 nmol/L 5-HT and greater than 300 nmol/L TXA2 (IC50), which already produced a nearly complete direct relaxation of the vessel preparations (EC50: 30 nmol/L). It is concluded that a significant spasmolytic action of prostacyclins against platelet-derived vasoconstrictors in vivo might only be obtained at concentrations that already produce considerable direct effects on vessel tone.