The effect of pentoxifylline (Trental) and two analogues, BL 194 and HWA 448, on the release of plasminogen activators and von Willebrand factor in rats.
The effects on fibrinolytic components of pentoxifylline (Trental), of its first metabolite BL 194 (penthydroxyfylline), and of its analogue HWA 448 (torbafylline) were studied in rats. BL 194, though not pentoxifylline and HWA 448, significantly enhanced the induced release by platelet-activating factor (PAF) of tissue-type plasminogen activator (tPA) from isolated perfused rat hindlegs. In contrast, the simultaneously induced release of von Willebrane factor (vWF) was reduced by BL 194. The effect of BL 194 on PAF-induced release of tPA and vWF could be mimicked by isobutyl-methylxanthine (IBMX), an inhibitor of phosphodiesterases. In vivo, BL 194 and pentoxifylline did not affect baseline levels of plasma tPA and PA inhibitor activity, nor did these compounds affect the in vivo induction of tPA release by PAF. Similarly, the induction by endotoxin of PA inhibitor activity was not influenced by pentoxifylline or BL 194. By its opposite effects on tPA and vWF release. BL 194 might favrorably influence the thrombotic balance.
Tranquille
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Gaubius Institute TNO, Leiden, The Netherlands.
Emeis
J J
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005342:Fibrinolysis / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply; D066298:In Vitro Techniques; D008297:Male; D010431:Pentoxifylline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
D004731:Endotoxins; D014841:von Willebrand Factor; C061298:torbafylline; D010959:Tissue Plasminogen Activator; C025189:lisofylline; D001920:Bradykinin; D010431:Pentoxifylline; D015056:1-Methyl-3-isobutylxanthine