Pharmacological observations of plasminogen activator release caused by vasoactive agents in isolated perfused pig...

Influences of vasoactive agents on plasminogen activator release (PA release) and perfusion pressure (PP) were studied in isolated perfused pig ears. The pig ear was perfused with oxygenated Tyrode's solution, pH 7.4, at 37 degrees C via the main artery and the perfusate from the veins was collected at 2-min intervals. The drug was injected into a rubber tube connected in the front of arterial cannula, and the fibrinolytic activity in the collected perfusate was measured by the fibrin plate method. Acetylcholine, bradykinin, and histamine enhanced PA release in a dose-dependent fashion (0.1-3.0 micrograms). Purified human thrombin also enhanced PA release in a dose-dependent fashion (1.5-12 U). In coronary vasodilators, dilazep caused a dose-dependent increase of PA release (10-100 micrograms) and dipyridamole caused a slight increase at a dose of 300 micrograms. However, nitroglycerin, papaverine, diltiazem, and trapidil did not exert any effects on PA release and neither did adenosine and ATP. Vasoconstricting agents, namely, epinephrine, norepinephrine, phenylephrine, and serotonin exerted hypertensive effects in a dose-dependent fashion (0.1-3.0 micrograms); however, they did not cause measurable increases of PA release. These results suggest that vasodilating substances may be essential for the enhancement of PA release from vascular bed.