Mechanism of A23187-induced airway obstruction in the guinea pig

Exposure of conscious guinea pigs to A23187 aerosol produced a concentration-related increase of excised lung gas volume (ELGV), . ., postmortem pulmonary gas trapping. Measurements of ELGV were highly correlated with measurements of dynamic compliance (C_dyn) and total pulmonary resistance (R_L) and were used as an indication of airway obstruction. We pretreated guinea pigs intravenously with the following drugs: atropine; LY163443, a selective LTD₄/E₄ antagonist; indomethacin; propranolol; and pyrilamine. The guinea pigs were exposed for 8 minutes to the A23187 aerosol, and ELGV measurements were then made. Atropine or pyrilamine prevented the A23187-induced gas trapping. Indomethacin or propranolol tended to potentiate the response and when combined, they potentiated the gas trapping by 80%. LY163443 had no effect alone, but when combined with indomethacin, propranolol, and pyrilamine, inhibited A23187-induced gas trapping by 67%. We conclude that cholinergic and histaminergic mechanisms play major roles in the ionophore-induced pulmonary gas trapping of the guinea pig. With appropriate pretreatment, sulfidopeptide leukotrienes may produce a substantial effect.