Arachidonic acid evokes epithelium-dependent relaxations in canine airways.
Responses to arachidonate were examined in rings with and without epithelium of lobar, segmental, and subsegmental canine bronchi. Arachidonate evoked epithelium-dependent relaxations, which were less pronounced in subsegmental bronchi and abolished by indomethacin and meclofenamate. Nordihydroguairetic acid (NDGA) and nafazatrom reduced epithelium-dependent relaxations only in lobar but unmasked epithelium-independent relaxations to arachidonate in all bronchi. Prostaglandin E2 and prostacyclin relaxed all tissues similarly. In lobar bronchi without epithelium, basal release of prostaglandin E2 was reduced by indomethacin but unaffected by NDGA. Arachidonate augmented prostaglandin E2 release more in subsegmental than in lobar bronchi with epithelium; in bronchi without epithelium the rise was absent (lobar) or attenuated (subsegmental). Arachidonate augmented the release of 6-ketoprostaglandin F1 alpha more in lobar bronchi with than without epithelium; this was inhibited by indomethacin, but not NDGA. Thus arachidonate releases prostaglandin E2 (possibly produced by cyclooxygenase inaccessible to inhibitors and activated by lipoxygenase products) but not prostacyclin from the epithelium. Heterogeneity in response to arachidonate is not due to different sensitivity to, or production of, prostaglandins.
Stuart-Smith
K
K
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 55905.
Vanhoutte
P M
PM
D000818:Animals; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004285:Dogs; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D011464:Epoprostenol / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D015289:Leukotrienes; D016718:Arachidonic Acid; D011464:Epoprostenol; D001091:Arachidonate Lipoxygenases; D015232:Dinoprostone