Role of tachykinins in ozone-induced airway hyperresponsiveness to cigarette smoke in guinea pigs.
Acute exposure to ozone (O3) induces airway 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 (DeltaRL = 67 +/- 19%, DeltaCdyn = -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 (DeltaRL = 620 +/- 224%, DeltaCdyn = -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-48968, 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.
Wu
Z X
ZX
Department of Physiology, University of Kentucky, Lexington, Kentucky 40536, USA.
Morton
R F
RF
Lee
L Y
LY
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001980:Bronchi / Q000187:drug effects; D016535:Bronchial Hyperreactivity / Q000139:chemically induced*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects; D064729:Neurokinin-1 Receptor Antagonists; D010126:Ozone / Q000633:toxicity*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D013373:Substance P / Q000037:antagonists & inhibitors / Q000502:physiology; D015320:Tachykinins / Q000502:physiology*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D064729:Neurokinin-1 Receptor Antagonists; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; D014028:Tobacco Smoke Pollution; D013373:Substance P; D010126:Ozone; D000109:Acetylcholine