Journal of Applied Physiology, Vol 75, Issue 3 1110-1116, Copyright © 1993 by American Physiological Society
Importance of prostanoids in calcium chelator-induced airway constriction
K. S. Lindeman, N. Downey, M. C. Liu, W. C. Hubbard, A. Kagey-Sobotka and C. A. Hirshman
Department of Environmental Health Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
To elucidate the mechanism of calcium chelator-induced airway constriction,
we examined the relationship between prostanoids and histamine in
bronchoalveolar lavage (BAL) fluid and the magnitude of airway constriction
in peripheral airways of anesthetized Basenji-Greyhound dogs. A wedged
bronchoscope technique was used to measure collateral system resistance
(Rcs) before and after aerosol challenges. Sublobar segments were
challenged either with acetylcholine or with Na2EDTA in the presence or
absence of meclofenamate sodium (3 mg/kg iv) or methylprednisolone (2
mg.kg-1.day-1). After measurements of Rcs, BAL was performed, and the fluid
was analyzed for prostanoids with the use of gas chromatography-mass
spectrometry. Sublobar segments challenged with Na2EDTA showed increased
concentrations of prostaglandin (PG) D2 but no increases in PGE2, PGF2
alpha, 9 alpha,11 beta-PGF2, 6-keto-PGF1 alpha, thromboxane B2, or
histamine. There was a strong relationship (r = 0.84, P = 0.005) between
changes in Rcs after Na2EDTA and concentrations of PGD2 in BAL fluid.
Acetylcholine, which increased Rcs to a similar degree as Na2EDTA did,
produced no significant increase in prostanoid concentrations. Changes in
Rcs after Na2EDTA and concentrations of PGD2 were reduced in the presence
of meclofenamate or methylprednisolone. These data support the idea that
the mechanism of calcium chelator-induced bronchoconstriction involves the
release of bronchoconstricting prostanoids.
