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

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Abstract
1 In anaesthetized guinea-pigs intravenous histamine caused an increase in airways resistance (RA) and a fall in dynamic compliance (CDyn). 2 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. 3 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. 4 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. 5 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 β-adrenergic system is not required for the effect of indomethacin on RA. No confirmation for lipoxygenase involvement was obtained with the lipoxygenase inhibitor, BW755.