In vivo metabolism of dihomo-γ-linolenic acid to bronchoactive products in the canine lung

We investigated the effects of dihomo-γ-linolenic acid (DGLA), the fatty acid precursor to the monoenoic prostaglandins, on pulmonary mechanics in the intact chest, artificially ventilated dog. Under conditions of normal airway tone, intravenously administered DGLA produced a modest, dose-related increase in lung resistance and decrease in dynamic lung compliance. These responses were approximately 30-100 times less than those produced by arachidonic acid. The bronchoconstrictive responses to DGLA were abolished by prior inhibition of the cyclooxygenase with indomethacin. PGD₁ was equal in activity to PGF_1α in causing constriction of central and peripheral airways of the dog. PGE₁ was without significant airway effects in these animals under conditions of resting airway tone. We conclude that DGLA is a moderately good substrate for the cyclooxygenase pathway enzymes of the canine lung, producing products having a predominantly bronchoconstrictive effect. This bronchoconstriction is most likely due to the synthesis of PGD₁ and PGF_1α and is not due to the synthesis of lipoxygenase pathway products.