We examined the effect of
AH 21-132, which has been reported to relax airway smooth muscle and inhibit
platelet activating factor (PAF)-induced airway hyperreactivity, on
ozone-induced
airway hyperresponsiveness (AHR) with airway
inflammation in dogs. Airway responsiveness (AR) to
methacholine was measured by modified Astograph (7 Hz oscillation method) before and after
ozone exposure, and the numbers of neutrophils in the peripheral blood and total cell counts, differential cell counts and TXB2 in BALF were measured before and after
ozone exposure.
Ozone exposure was carried out for 2 hr at an
ozone level of 3.46 +/- 0.10 ppm (mean +/- SE). There was a significant increase in AR to
methacholine after
ozone exposure (p less than 0.01), and the numbers of neutrophils in the peripheral blood and the total cell and neutrophil counts in BALF increased significantly (p less than 0.05). Pretreatment with
AH 21-132 at an oral dose of 20 mg/kg significantly prevented the
ozone-induced AHR to
methacholine (p less than 0.01), and also inhibited the increase of neutrophil counts in the peripheral blood, and the total cell counts and the neutrophil counts in BALF after
ozone exposure. There was no significant change in the levels of TXB2 in BALF before and after
ozone exposure. In dogs not exposed to
ozone, AR to
methacholine and respiratory resistance to
methacholine significantly decreased after administration of
AH 21-132 at an oral dose of 20 mg/kg (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)