Vagal mechanisms and the effect of indomethacin on bronchoconstrictor stimuli in the guinea-pig.

1. In urethane-anaesthetized guinea-pigs, under spontaneous respiration, indomethacin (1 mg kg-1 i.v., 10-45 min) approximately doubled the bronchoconstrictor effect (increase in airways resistance, R(aw)) of equieffective doses of histamine and 5-hydroxytryptamine (5-HT), but not that of acetylcholine or leukotriene D4 (LTD4). 2. In mechanically ventilated guinea-pigs indomethacin increased R(aw) responses to histamine as well as increasing the fall in dynamic compliance (Cdyn) evoked by this agent. 3. Cooling the cervical vagi, to temperatures shown to block efferent and probably afferent pathways (approximately 9 degrees C), abolished the effect of indomethacin on airways responses. Inhibition of indomethacin-induced hyperreactivity was also observed after vagal section. 4. Electrical stimulation of the peripheral vagus (1-20 Hz, 0.75-5 ms pulses) increased R(aw) and decreased Cdyn but these responses were not markedly altered by indomethacin. 5. It was concluded that the indomethacin-induced hyperreactivity of tracheal smooth muscle, which was demonstrated in vitro, may not account for the airways hyperreactivity observed in the present in vivo experiments. The hyperreactivity to histamine induced by indomethacin in vivo depends on the functional integrity of vagal reflex pathways.