Mh. Vargas et al., CHRONIC EXPOSURE TO OZONE CAUSES TOLERANCE TO AIRWAY HYPERRESPONSIVENESS IN GUINEA-PIGS - LACK OF SOD ROLE, Journal of applied physiology, 84(5), 1998, pp. 1749-1755
Tolerance to respiratory effects of O-3 has been demonstrated for anat
omic and functional changes, but information about tolerance to O-3-in
duced airway hyperresponsiveness (AHR) is scarce. In guinea pigs expos
ed to air or O-3 (0.3 parts/million, 4 h/day, for 1, 3, 6, 12, 24, or
48 days, studied 16-18 h later), pulmonary insufflation pressure chang
es induced by intravenous substance P (SP, 0.032-3.2 mu g/kg) were mea
sured, then the animals were subjected to bronchoalveolar lavage (BAL)
. Bronchial rings with or without phosphoramidon were also evaluated 3
h after air or a single O-3 exposure. O-3 caused in vivo AHR (increas
ed sensitivity) to SP after 1, 3, 6, 12, and 24 days of exposure compa
red with control. However, after 48 days of exposure, O-3 no longer ca
used AHR. Total cell, macrophage, neutrophil, and eosinophil counts in
BAL were increased in most O-3-exposed groups. When data from all ani
mals were pooled, we found a highly significant correlation between de
gree of airway responsiveness and total cells (r = 0.55), macrophages
(r = 0.54), neutrophils (r = 0.47), and eosinophils (r = 0.53), sugges
ting that airway inflammation is involved in development of AHR to SP.
Superoxide dismutase (SOD) levels in BAL fluids were increased (P < 0
.05) after 1, 3, 6, and 12 days of O-3 exposure and returned to basal
levels after 24 and 48 days of exposure. O-3 failed to induce hyperres
ponsiveness to SP in bronchial rings, and phosphoramidon increased res
ponses to SP in air-and O-3-exposed groups, suggesting that neutral en
dopeptidase inactivation was not involved in O-3-induced AHR to SP in
vivo. We conclude that chronic exposure to 0.3 ppm O-3, a concentratio
n found in highly polluted cities, resulted in tolerance to AHR to SP
in guinea pigs by an SOD-independent mechanism.