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

Article date: February 1984

By: T. P. Clay, D. C. Fenske in Volume 81, Issue 2, pages 335-339

A method is described in which changes in intrapulmonary airway tone of guinea‐pig isolated lungs are reflected by changes in intraluminal perfusion pressure.

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.

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.

Indomethacin, phenylbutazone and aspirin induced augmentation of the elevated perfusion pressure due to histamine, whereas BW755C did not.

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.

A method is described in which changes in intrapulmonary airway tone of guinea‐pig isolated lungs are reflected by changes in intraluminal perfusion pressure.

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.

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.

Indomethacin, phenylbutazone and aspirin induced augmentation of the elevated perfusion pressure due to histamine, whereas BW755C did not.

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.

DOI: 10.1111/j.1476-5381.1984.tb10083.x

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