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

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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 \gZ-cyclo-(Lys1-Gly6)-BK = \gZ-cyclo-kallidin > BK > kallidin = methionyllysyl-BK≫des-Arg9-BK. The same order was seen for skin responses in day 21, rheumatoid-arthritic rats. Mepyramine, 10 mg · 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 > methionyl-lysyl-BK > BK >> Z-cyclo-(Lys1-Gly6)-BK = Z-cyclo-kallidin>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. Neither of these fragments possessed agonist or antagonist action against BK in guinea-pig or rabbit skin. The B1. receptor antagonist, des-Arg9-Leu8-BK, had no effect against BK-induced responses in any of the models used. It is concluded that the kinin receptor mediating the increase in paw volume of rat and the increase in vascular permeability in rat, rabbit and guinea-pig is not of the B1-type. The difference in effects of the cyclic kinins and the modified kinin fragments may reflect a difference in the receptor mediating paw oedema and skin permeability in the rat compared to that mediating the same response in rabbit and guinea-pig skin. This requires further study.