Indomethacin enhances the effect of histamine on airways resistance in the anaesthetized guinea-pig.

In anaesthetized guinea-pigs intravenous histamine caused an increase in airways resistance (RA) and a fall in dynamic compliance (CDyn). Indomethacin (1 mg kg-1, i.v.) significantly enhanced the effect of histamine on RA. Indomethacin also increased the basal RA and the RA response to a histamine infusion. The effect of indomethacin on CDyn was less consistent but here also there was a trend for an increased response to histamine. Sodium carbonate (the vehicle for indomethacin, 0.05 ml 100 mM solution) had no effect on RA or CDyn in control experiments. Propranolol (0.1 mg kg-1, i.v.) enhanced the effect of histamine on RA in animals pretreated with either indomethacin or Na2CO3 vehicle, but the effect was more consistent in indomethacin pretreated animals. Indomethacin also tended to enhance the effect of histamine on RA in animals pretreated with reserpine or BW755c but it had little effect on the CDyn response to histamine. The results show that indomethacin augments the responsiveness of the airways to histamine in the anaesthetized guinea-pig. The results with propranolol and reserpine suggest that an operational beta-adrenergic system is not required for the effect of indomethacin on RA. No confirmation for lipoxygenase involvement was obtained with the lipoxygenase inhibitor, BW755.