The effects of arachidonic acid and non-steroidal anti-inflammatory drugs on intrapulmonary airways of the guinea-pig.
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 microM) 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.
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D008297:Male; D011458:Prostaglandins E / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011458:Prostaglandins E; D016718:Arachidonic Acid; D006632:Histamine