Role of cyclooxygenase products of arachidonic acid metabolism in Ascaris antigen-induced bronchoconstriction in sensitized dogs.
The pharmacologic modulation of Ascaris allergen-induced bronchoconstriction was investigated in beagle dogs sensitized by experimental infection with Ascaris suum ova. Ascaris-induced increases in total lung resistance (RL) and falls in dynamic lung compliance (Cdyn) were unaffected by pretreatment with an antihistamine (pyrilamine) given alone but were significantly attenuated (P less than .05) by the cyclooxygenase enzyme inhibitor, indomethacin. The combination of pyrilamine and indomethacin also produced a significant (P less than .01) inhibition of Ascaris-induced bronchoconstriction, greater than that produced by indomethacin given alone but the difference between the two treatment groups was not statistically significant. The combination of an antihistamine, the cyclooxygenase inhibitor indomethacin and the leukotriene synthesis inhibitor, U-60,257, almost completely abolished Ascaris-induced bronchoconstriction (91% inhibition of Cdyn changes; 93% inhibition of RL changes). The inhibition was significantly greater than that produced by cyclooxygenase inhibition alone. The leukotriene synthesis inhibitor piriprost (U-60,257) given alone or in combination with pyrilamine produced no inhibition of Ascaris-induced changes in RL or Cdyn. The leukotriene antagonist FPL55712 or the thromboxane synthase inhibitor U-63,557A also showed little or no activity in this model, whereas the thromboxane receptor antagonist AH23848 produced a marked inhibition of Ascaris-induced bronchoconstriction. We conclude that Ascaris-induced bronchoconstriction is mediated primarily by cyclooxygenase products of arachidonic acid metabolism. The role of histamine and lipoxygenase products can only be revealed during an effective cyclooxygenase blockade.
D000818:Animals; D000947:Antigens, Helminth; D001095:Arachidonic Acids / Q000502:physiology*; D001200:Ascaris / Q000276:immunology*; D001794:Blood Pressure / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004285:Dogs; D011464:Epoprostenol / Q000494:pharmacology / Q000031:analogs & derivatives; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008176:Lung Volume Measurements; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011738:Pyrilamine / Q000494:pharmacology; D012119:Respiration; D013189:SRS-A / Q000037:antagonists & inhibitors
D000947:Antigens, Helminth; D001095:Arachidonic Acids; D002867:Chromones; D013189:SRS-A; D006632:Histamine; C006312:FPL 55712; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D011738:Pyrilamine; C035296:piriprost; D007213:Indomethacin