Dry gas hyperpnea-induced bronchoconstriction in the guinea pig is
dependent on tachykinin-induced cysteinyl-leukotriene synthesis.
Yang, X. X., W. S. Powell, M. Hojo, and J. G. Martin.
Meakins-Christie Laboratories, McGill University Montreal, Quebec,
Canada H2X 2P2
APStracts 3:0494A, 1996.
The purpose of the study was to test the hypothesis that tachykinins
mediate hyperpnea-induced bronchoconstriction indirectly by
triggering cysteinyl-leukotriene (cys-LTs) synthesis in the airways.
Guinea pigs (350-600 gm) were anesthetized with xylazine and sodium
pentobarbital and received hyperpnea challenge (tidal volume=3.5-4ml,
frequency=150/min) with either humidified isocapnic gas (n=6), or dry
gas (n=7). Dry gas challenge was performed on animals that received
MK-571 (LTD4 antagonist; 2mg/kg, i.v.; n=5), capsaicin (n=4),
neurokinin antagonists (NK1 (CP-99994) + NK2 (SR-48968) 1mg/kg i.v.;
n=6) or the H1 antihistamine pyrilamine (2mg/kg i.v.; n=5). We
measured the tracheal pressure (Ptr) and collected bile for 1 hr
before and 2 hr after hyperpnea challenge. We examined the biliary
excretion of cys-LTs; the recovery of radioactivity in bile following
instillation of 1 [mu]Ci 3H-LTC4 intra-tracheally averaged 24% within
4 hours (n=2). The major cys-LT identified was LTD4 (32% recovery of
radioactivity). Cys-LTs were purified from bile of animals undergoing
hyperpnea challenge using reverse-phase HPLC and quantified by
radioimmunoassay. There was a significant increase in the peak value
of Ptr following challenge indicating bronchoconstriction in dry gas
challenged animals but not after humidified gas challenge. MK-571,
capsaicin, NK antagonists but not pyrilamine prevented the
bronchoconstriction. Cys-LT levels in the bile after challenge were
significantly increased from baseline in dry gas challenged animals
(P<0.05) and were higher than in the animals challenged with
humidified gas or dry gas challenged animals treated with capsaicin
or NK antagonists (P<0.01). The results indicate that
isocapnic dry gas hyperpnea induced bronchoconstriction is
leukotriene mediated and the role of tachykinins in the response is
indirect through release of leukotrienes. Endogenous histamine does
not contribute to the response.
Received 7 November 1995; accepted in final form 16 October 1995.
APS Manuscript Number A1177-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996