Induction of Increased Fibrinolytic Activator in Plasma by Various Drugs*)

Summary

Autonomic blocking agents failed to block the action of autonomic transmitters’ effect on F.A. increase in plasma. Autonomic blocking agents themselves caused the elevation of F.A. The depletion of catecholamines and serotonin, by reserpine and adrenalectomy, did not impair the ability of animals to produce enhanced F.A.level, nor did the removal of the spleen, kidney or hypophysis.

Many drugs were found to induce the increased F.A. level in plasma of animals, while others failed to do so. One common denominator of those drugs causing F.A. increase appears to be their ability to release histamine. Histamine was found to be an active agent in elevating F.A. and this action can sometimes be blocked by antihistaminics, as shown in a few experiments. The repeated injection of morphine, d-tubocurarine and compound 48/80, all showed the development of acute tolerance toward the hypotensive effect. The concomitant measurement of F.A. in plasma showed a parallel development of acute tolerance toward the F.A. level. There was a concomitant increase of histamine level, F.A. level and hematocrit value, after the single injection, each, of compound 48/80, morphine and d-tubocurarine. These results support our hypothesis that the F.A.in an animal, induced by various drugs, is caused either by histamine or a histamine release mechanism.

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