Vol. 89, Issue 5, 1949-1955, November 2000
Eicosanoid and muscarinic receptor blockade
abolishes hyperventilation-induced bronchoconstriction
Arthur N.
Freed,
Sharron
McCulloch, and
Yongqiang
Wang
Department of Environmental Health Sciences, School of Hygiene and
Public Health, The Johns Hopkins University, Baltimore, Maryland
21205
This study was
designed to test the hypothesis that hyperventilation-induced
bronchoconstriction (HIB) results from the combined effects of
prostanoid and leukotriene metabolism. A bronchoscope was used in
anesthetized dogs to record peripheral airway resistance and HIB before
and after combined treatment with inhibitors of cyclooxygenase
(indomethacin) and 5-lipoxygenase (MK-0591). Bronchoalveolar lavage
fluid (BALF) cells and mediators from hyperventilated and control
airways were also measured. Pretreatment with MK-0591 and indomethacin
significantly attenuated, but did not abolish, HIB. However, addition
of atropine nearly eliminated the residual response. Blockade of
eicosanoid metabolism markedly reduced the concentrations of
eicosanoids recovered in BALF after hyperventilation. Positive
correlations between posthyperventilation BALF prostanoid and
epithelial cell concentrations are suggestive of mucosal injury-induced mediator production and release. We conclude that HIB is prevented in
the presence of eicosanoid and muscarinic-receptor blockade and that
both classes of eicosanoids contribute similarly to the development of HIB.
asthma; canine; leukotrienes; mucosal injury; prostanoids
