Stimulation of prostacyclin production in blood vessels by the antithrombotic drug suloctidil.

Suloctidil is a calcium antagonist with vascular relaxing activity and an antithrombotic agent: its antiplatelet action has been demonstrated in vivo, but is difficult to reproduce in vitro and the mechanism of this effect remains unknown. We have observed that suloctidil (10 microM) stimulated the release of prostacyclin (PGI2) from the rabbit aorta, the dog vena cava and the dog portal vein, in vitro. This effect could be explained by an increased mobilization of free arachidonic acid. Neither the inactive congener CP894S, nor the two calcium channel antagonists, verapamil and flunarizine, reproduced the stimulatory effect of suloctidil. Suloctidil acted selectively on the vascular endothelium: it stimulated the release of PGI2 from bovine aortic and human umbilical vein endothelial cells, but neither from the de-endothelialized rabbit aorta nor from the bovine aortic media. The stimulatory effect of suloctidil on the release of the platelet inhibitor PGI2 from the vascular endothelium might contribute to the known antiplatelet and antithrombotic activity of this drug.