In the present study we have investigated some of the mechanisms underlying B(1)
kinin receptor-induced paw
edema formation in rats that had been treated with LPS, paying special attention to the involvement of
neurogenic inflammation. Intradermal (i.d.) injection of the B(1) receptor agonist des-Arg(9)-BK (100 nmol/paw) resulted in a marked increase in paw volume in animals pre-treated with LPS (0.40+/-0.06 ml). The co-injection of the selective NK(1)
FK888 (1 nmol/paw) or
NK(2)
SR 48968 (3 nmol/paw) receptor antagonists resulted in a significant inhibition of the
edema induced by des-Arg(9)-BK (30+/-4 and 25+/-7%, respectively). The NK(3)
SR 142801 (3 nmol/paw) antagonist did not demonstrate any significant effect on B(1) receptor-mediated paw
edema. The
edema induced by des-Arg(9)-BK was also significantly inhibited (33+/-5%) by the co-injection of the
CGRP-receptor antagonist CGRP 8-37 (1 nmol/paw) or by treatment of animals with
capsaicin (50 mgkg(-1), s.c., 48 h, prior) (45+/-4%). The pre-treatment of animals with
methysergide or with
mianserin, 5-HT(1) and 5HT(2) antagonists, respectively (both 10 mgkg(-1), i.p. 30 min), resulted in a significant reduction of the
edema mediated by B(1) receptors (23+/-5 and 20+/-3%, respectively). In addition,
compound 48/80 (12 microg/paw, 24 h) significantly reduced des-Arg(9)-induced paw
edema in rats pre-treated with LPS (23+/-3%), while the treatment of animals with the H(1) receptor antagonist
pyrilamine (10 mgkg(-1), i.
p., 30 min) failed to affect the edematogenic responses involving B(1) receptors. Finally, the co-injection of NOS inhibitors
L-NAME (100 nmol/paw) or 7-NINA (10 nmol/paw) did not affect the rat paw
edema caused by des-Arg(9)-BK, whereas they significantly inhibited BK-induced paw
edema. Jointly, the results of the present study show that the edematogenic response mediated by the activation of B(1) receptors, in animals pre-treated with LPS, involves the release of
tachykinins and CGRP, as well as
serotonin, while NO and
histamine seem not to be involved. Therefore, these data further support the notion that B(1) receptors have an important role in modulating the inflammatory processes.