PACAP reverses airway hyperresponsiveness induced by ozone exposure in guinea pigs

Background: We previously demonstrated that pituitary adenylate cyclase act ivating peptide (PACAP) inhibits airway smooth muscle contraction and plasm a extravasation. Objective: We thus hypothesized that PACAP may regulate ai rway responsiveness through these effects and examined the effects of exoge nously applied PACAP on the airway hyperresponsiveness induced by ozone exp osure. Methods: Ozone exposure was carried out in awake, spontaneously brea thing guinea pigs using 3 ppm for 2 h. Airway responsiveness to histamine w as determined before and 30 and 90 min after the termination of ozone expos ure for 2 h in anesthetized animals. Extravasation of Evans blue was measur ed before and 90 min after the termination of ozone exposure. Either PACAP (10(-6) mol/kg) or vehicle was administered intravenously 60 min after expo sure. The airway responsiveness was expressed as the concentration of hista mine required to produce a 200% increase in total pulmonary resistance (PC2 00). Results: Ozone exposure caused a significant decrease in PC200 (n = 5, p < 0.05) 30 min after ozone exposure which persisted 90 min thereafter, t hus suggesting that ozone caused airway hyperresponsiveness. PACAP signific antly suppressed the increase in airway hyperresponsiveness induced by ozon e 90 min after exposure (n = 5, p < 0.05). In contrast, this peptide did no t have any effect on plasma extravasation. Conclusion: We thus conclude tha t PACAP decreases ozone-induced airway responsiveness, and, therefore, intr avenously administered PACAP may be useful in reversing airway hyperrespons iveness. Copyright 1999 S. Karger AG, Basel.