Cholinergic mechanisms involved with histamine hyperreactivity in immune rabbit airways challenged with ragweed...

The present study examines the effects of aerosolized ragweed antigen (RAg) on tracheal (TSM) and bronchial (BSM) smooth muscle contraction in rabbits actively immunized with RAg. Airway segments were isolated 48 h after aerosol challenge with either saline or RAg, and airway contractile responses to histamine were measured. Histamine remained a weak agonist in TSM segments after RAg challenge. In contrast, BSM responsivity to histamine was significantly increased after RAg challenge as evidenced by a parallel shift to the left (i.e., Fslope = 3.2; degrees of freedom (df) = 1,224; p = NS and Felev = 19.4; df = 1,225; p less than 0.001) of the mean dose-response relationship. In sham-immunized rabbits, the BSM contractile responses to histamine were similar after aerosol challenge with either RAg or normal saline. After the BSM segments were treated with 10(-6) M atropine, there was no significant difference in histamine reactivity between the RAg- and saline-challenged groups. The augmented BSM contractile response to histamine was only partially inhibited in the presence of either tetrodotoxin or hexamethonium. We conclude that 48 h after a single in vivo exposure to antigen in immune rabbits, the airway contractile responses to histamine in vitro are increased in BSM but not in TSM and that the mechanism of the augmented contractile responses in BSM likely involves the facilitated neural release of acetylcholine from both preganglionic and postganglionic sites.