Eicosanoids modulate hyperpnea-induced bronchoconstriction in
canine peripheral airways.
Omori, Chiharu, Philip Tagari, and Arthur N. Freed.
Department of Environmental Health Sciences, The Johns Hopkins
University, 615 North Wolfe Street, Baltimore, Maryland 21205, The
First Department of Internal Medicine, Nihon University School of
Medicine, 30-1 Oyaguchikamimachi Itabashiku, Tokyo, 173 Japan,
Department of Biochemistry and Molecular Biology
APStracts 3:0269A, 1996.
We examined the role of leukotrienes (LTs) in the development of dry
air-induced bronchoconstriction (AIB) in canine peripheral airways.
Airway reactivity to exogenous LTs was first tested using an LTD4
aerosol challenge: peripheral airway resistance (Rp) increased
130+51% (n=4) above baseline when compared with its vehicle control.
AIB was then assessed by measuring Rp after, and airway wall
temperature (Taw) during, a dry air challenge (DAC). Treatment with a
peptidoleukotriene biosynthesis inhibitor (MK-0591) attenuated AIB by
65% without altering Taw. The fact that MK-0591 did not alter airway
reactivity to aerosolized acetylcholine and completely inhibited Ca2+
ionophore-induced LTB4 generation in canine whole blood attests to
the specificity of the drug. Treatment with MK-0591 did not effect
the increased number of epithelial cells recovered in bronchoalveolar
lavage fluid (BALF) 5 min after DAC. Concentrations of LTs and other
eicosanoids in BALF from vehicle-treated DAC airways were increased
above baseline values; only LTs were reduced by MK-0591. Before MK
-0591, AIB was significantly correlated with the dry air-induced
generation of LTC4-E4. After treatment with MK-0591, AIB was
correlated with Thromboxane B2, Prostaglandin (PG) F2" and PGE2.
We conclude that hyperpnea with dry air stimulates local production
and release of LTs in canine bronchi, and along with the generation
of bronchoconstricting and bronchodilating PGs, play a central role
in the modulation of AIB.
Received 6 December 1995; accepted in final form 1 April 1996.
APS Manuscript Number A1262-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 17 June 96