TY - JOUR
T1 - Role of tachykinins in ozone-induced airway hyperresponsiveness to cigarette smoke in guinea pigs
AU - Wu, Zhong Xin
AU - Morton, Robert F.
AU - Lee, Lu Yuan
PY - 1997/9
Y1 - 1997/9
N2 - Acute exposure to ozone (O3) induces air-way hyperresponsiveness to various inhaled bronchoactive substances. Inhalation of cigarette smoke, a common inhaled irritant in humans, is known to evoke a transient bronchoconstrictive effect. To examine whether O3 increases airway responsiveness to cigarette smoke, effects of smoke inhalation challenge on total pulmonary resistance (RL) and dynamic lung compliance (Cdyn) were compared before and after exposure to O3 (1.5 ppm, 1 h) in anesthetized guinea pigs. Before O3 exposure, inhalation of two breaths of cigarette smoke (7 ml) at a low concentration (33%) induced a mild and reproducible bronchoconstriction that slowly developed and reached its peak (ΔRL = 67 ± 19%, ΔCdyn = -29 ± 6%) after a delay of >1 min. After exposure to O3 the same cigarette smoke inhalation challenge evoked an intense bronchoconstriction that occurred more rapidly, reaching its peak (ΔRL = 620 ± 224%, ΔCdyn = -35 ± 7%) within 20 s, and was sustained for >2 min. By contrast, sham exposure to room air did not alter the bronchomotor response to cigarette smoke challenge. Pretreatment with CP-99994 and SR-48963, the selective antagonists of neurokinin type 1 and 2 receptors, respectively, completely blocked the enhanced responses of RL and Cdyn to cigarette smoke challenge induced by O3. These results show that O3 exposure induces airway hyperresponsiveness to inhaled cigarette smoke and that the enhanced responses result primarily from the bronchoconstrictive effect of endogenous tachykinins.
AB - Acute exposure to ozone (O3) induces air-way hyperresponsiveness to various inhaled bronchoactive substances. Inhalation of cigarette smoke, a common inhaled irritant in humans, is known to evoke a transient bronchoconstrictive effect. To examine whether O3 increases airway responsiveness to cigarette smoke, effects of smoke inhalation challenge on total pulmonary resistance (RL) and dynamic lung compliance (Cdyn) were compared before and after exposure to O3 (1.5 ppm, 1 h) in anesthetized guinea pigs. Before O3 exposure, inhalation of two breaths of cigarette smoke (7 ml) at a low concentration (33%) induced a mild and reproducible bronchoconstriction that slowly developed and reached its peak (ΔRL = 67 ± 19%, ΔCdyn = -29 ± 6%) after a delay of >1 min. After exposure to O3 the same cigarette smoke inhalation challenge evoked an intense bronchoconstriction that occurred more rapidly, reaching its peak (ΔRL = 620 ± 224%, ΔCdyn = -35 ± 7%) within 20 s, and was sustained for >2 min. By contrast, sham exposure to room air did not alter the bronchomotor response to cigarette smoke challenge. Pretreatment with CP-99994 and SR-48963, the selective antagonists of neurokinin type 1 and 2 receptors, respectively, completely blocked the enhanced responses of RL and Cdyn to cigarette smoke challenge induced by O3. These results show that O3 exposure induces airway hyperresponsiveness to inhaled cigarette smoke and that the enhanced responses result primarily from the bronchoconstrictive effect of endogenous tachykinins.
KW - Bronchoconstriction
KW - Bronchopulmonary C-fibers
KW - Inhaled irritants
KW - Neurokinin A
KW - Neurokinin receptor antagonists
KW - Substance P
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U2 - 10.1152/jappl.1997.83.3.958
DO - 10.1152/jappl.1997.83.3.958
M3 - Article
C2 - 9292485
AN - SCOPUS:0030761067
SN - 8750-7587
VL - 83
SP - 958
EP - 965
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
IS - 3
ER -