C. Bertrand et al., ROLE OF KININS IN THE VASCULAR EXTRAVASATION EVOKED BY ANTIGEN AND MEDIATED BY TACHYKININS IN GUINEA-PIG TRACHEA, The Journal of immunology, 151(9), 1993, pp. 4902-4907
Tachykinins released from sensory nerves mediate, at least in part, th
e plasma extravasation induced by allergen challenge to the airways of
sensitized guinea pigs. We investigated the role of kinins in this ac
tivation of sensory nerves. We found that the increase in Evans blue d
ye extravasation evoked by aerosol of bradykinin (100 muM, 2 min) in t
he presence of phosphoramidon (2.5 mg/kg, i.v.) was abolished complete
ly by the selective B2 bradykinin antagonist, HOE 140 (0.1 mumol/kg, i
.v.), and was inhibited (60%) by the selective NK1 tachykinin receptor
antagonist, CP-96,345 (2 mumol/kg, i.v.). Plasma extravasation evoked
by aerosolized substance P(10 muM/kg, 2 min) in presence of phosphora
midon was abolished by CP-96,345, but was not affected by HOE 140. The
extravasation of the Evans blue dye evoked by OVA (5%, 2 min) in sens
itized guinea pigs was reduced by HOE 140 (45%) when the animals were
perfused after 5 min and by 39% when perfusion was performed at 10 min
. In the presence of phosphoramidon, the response to OVA at 10 min was
reduced by 57% by HOE 140 and by 72% by CP-96,345. The combination of
CP-96,345 and HOE 140 did not further increase the inhibition obtaine
d with CP-96,345 alone. The results provide evidence that the activati
on of sensory nerves that contribute to Ag-evoked plasma extravasation
is due to kinin release. The contribution of this cascade of events m
ay be exaggerated in pathophysiologic conditions in which neutral endo
peptidase is down-regulated.