The effect of kinins on paw oedema and uterus in rats

Bradykinin (BK) produced a dose-related increase in the paw volume of the rat. Responses to BK at all doses used were not affected by pretreating the rats with diphenhydramine, 1 mg kg-1, or indomethacin, 2.5 and 5 mg kg-1. Indomethacin, 10 mg kg-1 produced a small but significant reduction in the responses to BK. Captopril 1 mg kg-1 enhanced responses to low but not to high doses of BK. The rank order of potency of various kinin analogues to increase paw volume was found to be methionyl-lysyl-BK (met-lys-BK) greater than BK greater than lysyl-BK (Kallidin) much greater than des-Arg9-BK. The B1-receptor antagonist des-Arg9-Leu8-BK did not affect responses to BK on paw volume. Two modified kinin fragments S2302 (H-D-Pro-Phe-Arg-p-Nitroaniline) and S2441 (H-D-Pro-Phe-Arg-NH-heptyl) produced dose-related increases in paw volume both having approximately half the potency of BK. These responses were not antagonised by diphenhydramine, 1 mg kg-1 which reduced significantly the response to histamine. On the isolated rat uterus the rank order of potency of various kinins was BK greater than Kallidin greater than met-lys-BK greater than des-Arg9-BK. The two modified kinin fragments S2302 and S2441 (but not des-Arg9-Leu8-BK) antagonised BK induced contractions of the rat uterus. From the rank order of potency studies the receptor mediating contraction of the rat uterus in vitro and increase in rat paw volume to BK appear to be of the same type.(ABSTRACT TRUNCATED AT 250 WORDS)