Summary
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 (μM) 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.
