Am. J. Respir. Crit. Care Med., Vol 149, No. 2, 02 1994, 387-391.
Involvement of tachykinin receptors (NK1 and NK2) in sodium metabisulfite-induced airway effects
T Sakamoto, H Tsukagoshi, PJ Barnes and KF Chung
Department of Thoracic Medicine, National Heart and Lung Institute, London, United Kingdom.
We have investigated the effects of CP-96,345 and SR-48968, new nonpeptide
(neurokinin) NK1 and NK2 receptor antagonists, respectively, against
bronchoconstriction and airway microvascular leakage induced by inhaled
sodium metabisulfite (MBS) in anesthetized guinea pigs. Lung resistance
(RL) was measured for 6 min after challenge, followed by measurement of
extravasation of Evans blue dye into airway tissues, used as an index of
airway microvascular leakage. MBS (80 mM, 30 breaths) caused a significant
increase in RL and leakage of dye at all airway levels. CP-96,345 (2 mg/kg,
intravenous) but not SR-48968 (1.5 mg/kg, intravenous) significantly
inhibited the leakage of dye at all airway levels except for trachea. Each
antagonist inhibited significantly the maximal increase in RL. The
combination had a significant additive effect against the
bronchoconstriction, when compared with SR-48968 alone, and significantly
inhibited the leakage of dye at the same airway levels as CP-96,345. We
conclude that bronchoconstriction induced by inhaled MBS is, at least
partly, mediated by activation of both NK1 and NK2 receptors, and the
airway microvascular leakage by NK1 receptor stimulation alone.
