Interaction between SIN-1 and prostacyclin in inhibiting platelet aggregation.
SIN-1, the metabolite of molsidomine, caused a dose-dependent inhibition of the aggregation of rabbit platelets induced by adenosine diphosphate (ADP) and the stable thromboxane mimetic U-46619. Molsidomine was inactive in this respect. In the presence of a threshold concentration of prostacyclin, the antiaggregating activity of SIN-1 became more pronounced. As a result, the dose-response curve of SIN-1 was shifted to the left. These findings suggest that SIN-1 could be of therapeutic value to suppress platelet aggregation during atherosclerotic disease when the endogenous supply of endothelium-derived relaxing factor is compromised.
Bult
H
H
Division of Pharmacology, University of Antwerp (UIA), Wilrijk, Belgium.
Fret
H R
HR
Herman
A G
AG
D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology*
D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D006152:Cyclic GMP