Acute release of plasminogen activator (PA) was studied in rat isolated hindleg system perfused with Tyrode solution. 2. Leukotriene C4 (LTC4) and LTD4 dose-dependently induced the release of PA, which plateaued at 160 nmol l-1 and 200 nmol l-1, respectively. The amount of PA released was about 1 iu ml-1. The effects of LTC4 and LTD4 were not additive. 3. The PA released was identified as tissue-type PA (t-PA) by quenching experiments using anti-human t-PA IgG, by fibrin autography, and by the dependence of its activity on the presence of soluble fibrin. 4. LTE4 (300 and 450 nmol l-1) and 5-hydroxy-eicosatetraenoic acid (600 nmol l-1) did not induce any t-PA release in the perfusion system used. 5. Release of t-PA induced by LTC4 and LTD4 was inhibited by the leukotriene-receptor antagonist FPL 55712 (10 mumol l-1), whereas FPL 55712 did not inhibit t-PA release induced by platelet-activating factor (Paf-acether). 6. In vivo LTC4 and LTD4 (2 micrograms kg-1 i.v.) also induced an acute increase of t-PA activity in rat blood as evidenced by decreased blood clot lysis times. 7. Prostaglandin E1 and E2, prostacyclin and the stable prostacyclin analogue ZK 36374 at concentrations of 0.1-3.0 mumol l-1 induced little or no t-PA release.
