Interactions between acetylcholine and substance P effects on lung mechanics in the rabbit

The pharmacological mechanisms involved in the acetylcholine (ACh)- and substance P (SP)-induced changes in pulmonary mechanics were studied in isolated perfused rabbit lungs. Tracheal pressure (Ptr) and airflow were measured by a Fleisch pneumotachograph and pressure transducers. Air volume, lung resistance (R(L)) and dynamic compliance (Cdyn) were calculated. ACh induced a dose-dependent increase in Ptr and R(L), and a decrease in Cdyn. These effects were strongly prevented by atropine, and partly by SR140333, a neurokinin NK1 receptor antagonist SR48968, a neurokinin NK2 receptor antagonist; indomethacin and antihistaminics and indomethacin did not protect the lungs against this drug. 5-hydroxytryptamine induced no significant change in lung mechanic parameters. Cumulative concentrations of histamine increased R(L) and decreased Cdyn. We conclude that ACh-induced changes in lung resistance and compliance are in part mediated by a direct effect on airway smooth muscle and in part by the stimulation of C fibers, by the release of histamine from mast cells and by the synthesis of arachidonic acid metabolites. In turn, the effects of SP on lung mechanics are partly due to cholinergic activation.