title: Prevention of ozone-induced airway hyperresponsiveness and epithelial injury by phosphodiesterase inhibitors in guinea pigs.
abstract: We investigated the effects of phosphodiesterase (PDE) inhibitors on ozone-induced airway hyperresponsiveness (AHR) in guinea pigs. Theophylline (10-100 mg/kg), rolipram (1-100 mg/kg) and T-440 (1-100 mg/kg) were orally administered 30 min before ozone exposure (3 ppm, for 30 min). Ozone exposure caused an increase in airway responsiveness to methacholine aerosol, and log PC(10) (log-transformed methacholine concentration causing a 10 cm H(2)O increase in pulmonary inflation pressure) in the control and ozone-exposed group was 4.43±0.05 (n=6) and 3.26±0.15 (n=12), respectively. Theophylline at 100 mg/kg, 10 mg/kg rolipram and 10 mg/kg T-440 significantly inhibited AHR with log PC(10) value of 4.73±0.16 (n=7), 3.74±0.11 (n=7), 3.82±0.15 (n=6), respectively. On histological examination, epithelial damage in the trachea and peripheral airways was recognized after ozone exposure. At 100 mg/kg, rolipram, T-440 and theophylline caused complete inhibition of AHR, and prevented epithelial damage of the trachea and peripheral airways. These results indicate that PDE inhibitors prevent not only ozone-induced AHR but also airway epithelial injury by ozone.
authors.affiliation: Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., 2-2-50, Kawagishi, Toda, Saitama 335, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Matsubara
authors.forename: K
authors.initials: K
authors.lastname: Fushimi
authors.forename: O
authors.initials: O
authors.lastname: Kaminuma
authors.forename: H
authors.initials: H
authors.lastname: Kikkawa
authors.forename: K
authors.initials: K
authors.lastname: Ikezawa
authors.forename: K
authors.initials: K
authors.lastname: Naito