Stimulation of the plasma fibrinolytic activity in rats by the prostacyclin analogue CG 4203.

In anesthetized rats the intravenous infusion (15-120 min) of the prostacyclin analogue CG 4203 (0.215-2.15 micrograms.kg-1.min-1) resulted in a time and dose dependent shortening of the ex vivo euglobulin clot lysis time (ECLT). This effect that appeared to be significant already in the non-hypotensive dose range of CG 4203, was still existing at 2 hours after cessation of the infusion. The phosphodiesterase inhibitor theophylline (4.64 mg.kg-1 i.v.) potentiated the ECLT shortening effect of CG 4203. Even the highest dose of CG 4203 did not change the plasma fibrinogen levels. In contrast to low molecular weight urokinase (100 PU/ml) CG 4203 (10 microM) did not shorten the in vitro lysis of preformed euglobulin clots from untreated rats nor did it reduce the 125J-fibrin content of human thrombi in the Chandler loop system. From these results it is concluded that intravenously infused CG 4203 increases the plasma fibrinolytic activity in rats by a c-AMP dependent mechanism, probably by release of plasminogen activator. Direct urokinase like activation of plasminogen does not occur with CG 4203. The relevance of this activity is discussed with respect to the CG 4203 treatment of occlusive vascular diseases.