A bradykinin antagonist inhibits carrageenan edema in rats

Abstract

Bradykinin has been implicated in acute inflammatory reactions. Intradermal injection elicits increased vascular permeability and hyperalgesia, and bioassays have suggested increased bradykinin concentration in inflammatory exudates. Poorly specific inhibitors of kallikrein, the enzyme catalyzing formation of bradykinin, inhibit certain acute inflammatory reactions. However, the lack of a specific bradykinin receptor antagonist has made proof of the hypothesis difficult. In this study, we have used the potent, specific bradykinin antagonist DArg[Hyp3DPhe7] bradykinin (NPC 567) as a probe to examine the role of bradykinin in carrageenan-induced edema in the paws of rats. Subplantar injection of carrageenan led to an increase in immunoreactive bradykinin and metabolic product, desArg9bradykinin. NPC 567 inhibited the development of edema in response to carrageenan, to a maximum 65%. Thus, bradykinin appears to be a major mediator of increased vascular permeability in response to carrageenan.