The effects of arachidonic acid and non-steroidal anti-inflammatory drugs on intrapulmonary airways of the guinea-pig

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Abstract
1 A method is described in which changes in intrapulmonary airway tone of guinea-pig isolated lungs are reflected by changes in intraluminal perfusion pressure. 2 A supramaximal dose of arachidonic acid (AA) (61 μm) was found to have little on no action on baseline perfusion pressure. However, following elevation of perfusion pressure with histamine, AA caused a dose-dependent pressure decrease. This was also mimicked by prostaglandin E1 (PGE1) and PGE2. 3 AA induced a reduction of histamine elevated perfusion pressure which was inhibited, dose-dependently, by several non-steroidal anti-inflammatory agents including indomethacin, phenylbutazone, aspirin, benoxaprofen, BW755C and phenidone. Their respective rank order of potency appeared to correlate with their activity against microsomal cyclo-oxygenase. 4 Indomethacin, phenylbutazone and aspirin induced augmentation of the elevated perfusion pressure due to histamine, whereas BW755C did not. 5 We suggest that the primary arachidonate metabolite present in intrapulmonary airways following histamine-induced constriction is probably a relaxant of the E series. However, our data suggest that both cyclo-oxygenase and lipoxygenase products are associated with the maintenance of airway tone.