Repeated challenge with dinitrobenzene sulphonic acid in dinitrofluorobenzene-sensitized mice results in vascular hyperpermeability in the trachea: A role for tachykinins

1. This study investigates the role of tachykinins in a repeated challenge with dinitrobenzene sulphonic acid (DNS) on the tracheal vascular permeability in dinitrofluorobenzene (DNFB)sensitized mice. 2. DNFB-contact sensitization was followed by an intranasal (i.n.) challenge with DNS. A second challenge with DNS was administered 24 h after the first challenge. To assess changes in tracheal vascular permeability, Evans blue dye accumulation in tracheal tissue was measured. 3. A repeated challenge with DNS in DNFB-sensitized mice led to a 2.8 fold increase in tracheal vascular permeability when compared to DNFB-sensitized and vehicle-challenged mice or a 2.5 fold increase when compared to DNFB-sensitized single DNS-challenged mice (P < 0.001, ANOVA). 4. RP67580 (10^-9 mol mouse^-1 i.v.) reduced the increased tracheal vascular permeability induced by a second exposure to DNS in DNFB-sensitized mice completely when injected 15 min before the second challenge (P < 0.001, ANOVA). 5. The increased tracheal vascular permeability response induced by the second exposure to DNS could be mimicked with i.n. application of capsaicin (10^-10 mol mouse^-1) or substance P (SP) (10^-12 mol mouse(-1)) to DNFB-sensitized and single DNS-challenged mice. 6. These results suggest that both tachykinin NK₁ receptors and sensory nerves are involved in the development of vascular hyperpermeability changes found in the trachea of DNFB-sensitized mice after a repeated DNS-challenge.