Effect of anti‐proteases and hexadimethrine bromide on the release of a bradykinin‐like substance during heating (46° C) of rat paws

Abstract

1 The conditions in which the release of an active, bradykinin-like agent occurred when rat paws were heated to 46° C were studied by means of the double coaxial perfusion of the subcutaneous spaces. 2 The active material thus released stimulated the isolated rat uterus, produced a relaxing effect on the isolated rat duodenum, was destroyed by incubation with chymotrypsin and was potentiated by bradykinin-potentiating factor. LSD-25, in doses sufficient completely to block 5-hydroxytryptamine, did not affect the responses of the isolated uterus to the active material. 3 The effects on this release of anti-proteases and hexadimethrine bromide, atropine and diphenhydramine were studied. 4 Soy-bean trypsin inhibitor and hexadimethrine bromide added to the perfusion fluid produced a potent and reversible inhibition of the release of the active material; aprotinin and Kunitz inhibitor caused a temporary block. 5 When administered intravenously, much larger doses of the substances were necessary to produce a similar block. 6 Pretreatment of the animals with atropine plus diphenhydramine did not affect the release of the active kinin(s). 7 Ligature of one iliac artery was followed by disappearance of the active material in the perfusate from the corresponding paw. 8 These facts suggest that heating elicits a process leading to plasma extravasation and that the subcutaneous tissue is the chief site of release of the active material.