The antibradykinin action of fibrinolysin and other studies on capillary permeability employing different mediators and synthetic bradykinin

The Rat Plasminogen System, Intrahepatic Fibrinolysis and Carbon Tetrachloride Hepatotoxicity

“…Enhanced intrahepatic fibrinolysis did not follow small doses of SK or trypsin (Table 2); indeed the fibrinolytic activity was somewhat lower than normal following low SK or trypsin dosage. Copley (41), Ascheim (42) and one of us have (43) reported that plasmin can decrease vascular and tissue permeability. The pro-coagulant, antiinflammatory effect of protease in low dosage is entirely consistent with decreased vascular, tissue and cellular permeability, and, indeed, may even account for it.…”

Interrelationship of Human Plasma Kallikrein and Plasmin in Inflammation

“…In fact capillary permeability induced by kalbdin-9 is inhibited by intravenous administration of plasmin in rats and guinea pigs [94] by oral administration of streptokinase mixed with human plasma in rabbits [95] and by simultaneous intradermal injection of kallidin-9 and plasmin [96]. Preplasmin, on the other band, was found to produce an increase in capillary permeability which, like that of kallidin-9, could be suppressed by the simultaneous injection of plasmin [7].…”

“…In electron microscope studies of the skin capillaries of the guinea pig, it has been observed [122] that the injection of kallidin-9 causes a marked discontinuity of the endothelium (with intact subendothelial membrane) and it has been suggested [96] that the previous adminis tration of plasmin caused molecular breakdown products of fibrin to accumulate, blocking the pores or channels in the basement mem brane, and thus decreasing permeability to inflammatory stimuli and to kallidin-9.…”

“…Preplasmin, on the other band, was found to produce an increase in capillary permeability which, like that of kallidin-9, could be suppressed by the simultaneous injection of plasmin [7]. Although the intravenous injection of either preplasmin or kallidin-9 followed by the intradermal injection of the opposite agent resulted in a moderate decrease of capillary perme ability, their simultaneous injection resulted in an increase in permeability [96]. These apparent anomalous findings may well be due to the presence of other plasma components in the preplasmin preparation, i.e., plasma kallikrein or its activator.…”

“…The mechanism of their action is still not fully understood. Three main mechanisms have been proposed: (1) At the site of in flammation the enzymes prevent the deposition of fibrin or other macromolecules around the inflammed area, thus preventing the accumulation of exudate and permitting the multiple defensive forces of the bood to counteract the inflammatory stimuli [132]; (2) the enzymes produce their inflammatory response by increasing the inhibitor levels in the blood [114,133], and (3) the breakdown products of fibrin obstruct the pores or channels in the basement membrane thus preventing the increased capillary permeability produced by the inflammatory response [96].…”