Modulation of prostacyclin/thromboxane formation by molsidomine during platelet-endothelial cell interactions.
Platelet and endothelial cell metabolism of both exogenous and endogenous arachidonic acid, via the cyclooxygenase pathway, was evaluated according to thromboxane and prostacyclin formations. This was investigated in platelets, endothelial cells alone or during their interactions, in the presence or absence of SIN-1, the active anti-anginal metabolite of molsidomine. This revealed that, in contrast to the generation of thromboxane, which was decreased in the presence of endothelial cells, especially from endogenous arachidonate, that of prostacyclin increased under basal conditions as well as from endogenous arachidonate, that of prostacyclin increased under basal conditions as well as from endogenous arachidonate to a lesser extent. SIN-1 reduced thromboxane formation solely from endogenous arachidonate, and this was more pronounced when both cell populations interacted. In contrast, SIN-1 failed to decrease prostacyclin formation, which would emphasize its anti-aggregating potential. We conclude that the liberation of arachidonic acid leading to prostanoid synthesis may be differently regulated in platelets and endothelial cells, and that molsidomine might be a potential anti-aggregating drug in altering specifically thromboxane formation.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D002450:Cell Communication; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013931:Thromboxanes / Q000096:biosynthesis*
D001095:Arachidonic Acids; D013931:Thromboxanes; D016718:Arachidonic Acid; C002385:linsidomine; D008981:Molsidomine; D011464:Epoprostenol