Synergistic disaggregation of platelets by tissue-type plasminogen activator, prostaglandin E1, and nitroglycerin.
Endothelial cells produce at least three substances that can attenuate the platelet aggregation response: tissue-type plasminogen activator; the platelet inhibitory prostaglandins I2 and E1; and endothelium-derived relaxing factor, one form of which exhibits properties of nitric oxide. Since platelet aggregates formed in vivo are involved in the initiation of many clinically important occlusive vascular syndromes, we tested the hypothesis that these endothelial products act synergistically to disperse platelet aggregates. Our data reveal that tissue-type plasminogen activator, prostaglandin E1, and nitroglycerin (an organic nitrate activator of guanylate cyclase analogous to endothelium-derived relaxing factor) act synergistically to disaggregate platelets and do so in part by modulation of platelet cyclic nucleotides. These data suggest a potential mechanism by which the endothelium protects against the formation of platelet aggregates in vivo and offer a potential strategy for improving the efficacy of thrombolytic therapy.
Stamler
J S
JS
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Vaughan
D E
DE
Loscalzo
J
J
D000527:Alprostadil / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008433:Mathematics; D008962:Models, Theoretical; D005996:Nitroglycerin / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D010959:Tissue Plasminogen Activator; D000527:Alprostadil; D005996:Nitroglycerin