Receptors mediating the increase in vascular permeability to kinins: comparative studies in rat, guinea-pig and rabbit

Abstract

The effect of bradykinin (BK) and a variety of kinin analogues and modified kinin fragments were assessed in several models representing the vascular permeability aspect of the inflammatory response. The rank order of potency of various kinin analogues to increase paw volume and skin vascular permeability in rats was sigma-cyclo-(Lys1-Gly6)-BK = sigma-cyclo-kallidin much greater than BK greater than kallidin = methionyl-lysyl-BK much greater than des-Arg9-BK. The same order was seen for skin responses in day 21, rheumatoid-arthritic rats. Mepyramine, 10 mg X kg-1 almost completely inhibited rat skin vascular responses to histamine, had no effect on BK and produced a small but significant inhibition of the responses to both cyclic-kinins. A different rank order of potency for the kinins was produced in both the guinea-pig and rabbit skin; this being kallidin greater than methionyl-lysyl-BK greater than BK much much greater than sigma-cyclo-(Lys1-Gly6)-BK = sigma-cyclo-kallidin greater than des-Arg9-BK. Neither of the cyclic kinins antagonised BK-induced increases in skin vascular permeability in guinea-pig or rabbit. Two modified kinin fragments, D-Pro-Phe-Arg-paranitroaniline and D-Pro-Phe-Arg-heptylamide, which have previously been demonstrated to be putative B2 receptor antagonists on in vitro tissues, enhanced the effect of BK in rat skin and when injected alone produced dose-related increases in skin vascular permeability in normal and rheumatoid-arthritic rats both having approximately half the potency of BK.(ABSTRACT TRUNCATED AT 250 WORDS)