PACAP reverses airway hyperresponsiveness induced by ozone exposure in guinea pigs

Background: We previously demonstrated that pituitary adenylate cyclase activating peptide (PACAP) inhibits airway smooth muscle contraction and plasma extravasation. Objective: We thus hypothesized that PACAP may regulate airway responsiveness through these effects and examined the effects of exogenously applied PACAP on the airway hyperresponsiveness induced by ozone exposure. Methods: Ozone exposure was carried out in awake, spontaneously breathing guinea pigs using 3 ppm for 2 h. Airway responsiveness to histamine was determined before and 30 and 90 min after the termination of ozone exposure for 2 h in anesthetized animals. Extravasation of Evans blue was measured before and 90 min after the termination of ozone exposure. Either PACAP (10^-6 mol/kg) or vehicle was administered intravenously 60 min after exposure. The airway responsiveness was expressed as the concentration of histamine required to produce a 200% increase in total pulmonary resistance (PC₂₀₀). Results: Ozone exposure caused a significant decrease in PC₂₀₀ (n = 5, p < 0.05) 30 min after ozone exposure which persisted 90 min thereafter, thus suggesting that ozone caused airway hyperresponsiveness. PACAP significantly suppressed the increase in airway hyperresponsiveness induced by ozone 90 min after exposure (n = 5, p < 0.05). In contrast, this peptide did not have any effect on plasma extravasation. Conclusion: We thus conclude that PACAP decreases ozone-induced airway responsiveness, and, therefore, intravenously administered PACAP may be useful in reversing airway hyperresponsiveness.