An. Freed et al., Antioxidant transport modulates peripheral airway reactivity and inflammation during ozone exposure, J APP PHYSL, 87(5), 1999, pp. 1595-1603
We examined the effects of ozone (O-3) and endogenous antioxidant transport
on canine peripheral airway function, central airway function, epithelial
integrity, and inflammation Dogs were either untreated or pretreated with p
robenecid tan anion-transport inhibitor) and exposed for 6 h to 0.2 parts/m
illion O-3 Peripheral airway resistance (Rpa) and reactivity (Delta Rpa) we
re monitored in three sublobar locations before and after exposure to eithe
r air or O-3. Pulmonary resistance and transepithelial potential difference
in trachea and bronchus were also recorded. Bronchoalveolar lavage fluid (
BALF) was collected before, during, and after exposure. O-3 increased Rpa a
nd Delta Rpa only in probenecid-treated dogs and in a location-dependent fa
shion. Pulmonary resistance and potential difference in bronchus increased
after O-3 exposure regardless of treatment. O-3 markedly increased BALF neu
trophils only in untreated dogs. With the exception of hexanal, O-3 did not
alter any BALF constituent examined. Probenecid reduced BALF ascorbate, BA
LF protein, and plasma urate. We conclude that 1) a 6-h exposure to 0.2 par
ts/million O-3 represents a subthreshold stimulus in relation to its effect
s an peripheral airway function in dogs, 2) antioxidant transport contribut
es to the maintenance of normal airway tone and reactivity under conditions
of oxidant stress, 3) O-3-induced changes in Rpa and Delta Rpa are depende
nt on location, and 4) peripheral airway hyperreactivity and inflammation r
eflect independent responses to O-3 exposure. Finally, although anion trans
port mitigates the effect of O-3 On peripheral airway function, it contribu
tes to the development of airway inflammation and may represent a possible
target for anti-inflammatory prevention or therapy.