title: The role of cyclic nucleotides in the release of tissue-type plasminogen activator and von Willebrand factor.
abstract: The modulation of the induced acute release of tissue-type plasminogen activator (t-PA) and of von Willebrand factor (vWF) by compounds affecting cyclic nucleotide levels was studied, using an isolated rat hindleg perfusion system. Platelet-activating factor (PAF; 5 nM) or bradykinin (0.8 microM) were used to induce release of t-PA and vWF. The guanylate cyclase activators sodium nitroprusside and atrial natriuretic factor reduced the induced release of t-PA and vWF. Release was not affected by inhibiting nitric oxide production with NG-nitro-L-arginine. The effects of nitroprusside and atrial natriuretic factor could not be reproduced by infusion of 8-bromo-cGMP. The adenylate cyclase activator forskolin had no effect on bradykinin-induced release of t-PA and vWF, reduced PAF-induced t-PA release, but potentiated PAF-induced vWF release. These modulatory effects were only partially mimicked by infusion of 8-bromo-cAMP. None of the compounds tested was able to induce the release of t-PA or of vWF in the absence of stimulation by bradykinin or platelet-activating factor. Cyclic nucleotides can thus modulate, but not induce, the acute release of t-PA and vWF from perfused rat hindlegs.
authors.affiliation: Gaubius Laboratory IVVO-TNO, Leiden, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Tranquille
authors.forename: J J
authors.initials: JJ
authors.lastname: Emeis
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012636:Secretory Rate / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D010972:Platelet Activating Factor; D014841:von Willebrand Factor; D009599:Nitroprusside; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D010959:Tissue Plasminogen Activator; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D001920:Bradykinin