ACQUIRED RESISTANCE TO THE PHARMACOLOGIC EFFECTS OF PLASMIN: STUDY ON TACHYPHYLACTOGENIC PROTEINS

¹ Roswell Park Memorial Institute and the Graduate School of Arts and Sciences, University of Buffalo, Buffalo, New York

Intravenous administrations of high doses of human plasmin into dogs resulted in hypotension, afibrinogenemia, and leukopenia. Successive rapid injections of plasmin administered within a short period of time resulted in a progressive decrease and eventual abolishment of the hypotensive response.

This tachyphylaxis developed rapidly, was drug specific, and persisted, in part, for at least twenty-four hours. Resistance toward the fibrinogenolytic effect of plasmin was sustained for longer time intervals.

Tachyphylaxis toward the hypotensive response was found, by blood exchange techniques, to be reversible. The reversibility suggests a mechanism of saturation of specific receptors by either plasmin or a bradykinin-like vasodilator polypeptide formed in vivo by plasmin action.

Studies are in progress to elucidate the relationship between plasmin and the kallikrein-kallidin system.