Analysis of airway responses to dihomo-γ-linolenic acid in the cat

Responses to the monoenoic prostaglandin (PG) precursor, dihomo-γ-linolenic acid, and the monoenoic PGs, PGF₁(α) and PGD₁, were investigated in the airways of mechanically ventilated paralyzed cats. Under resting airway smooth muscle tone conditions, i.v. injections of dihomo-γ-linolenic acid increased lung resistance, decreased dynamic compliance and increased the frequency dependence of compliance. Airway responses to the monoenoic precursor were dose-dependent and were blocked by sodium meclofenamate, a cyclooxygenase inhibitor. Intravenous injections of PGD₁ or PGF₁(α) caused qualitatively similar changes in lung mechanics. The corresponding bisenoic PGs, PGD₂ PGF₂(α) and their precursor, also increased lung resistance, decreased dynamic compliance and increased the frequency dependence of compliance. These substances were 3- to 10-fold more potent than were the monoenoic agents. However, when airway smooth muscle tone was enhanced with serotonin, the response to dihomo-γ-linolenic acid was characterized by a sustained reduction in lung resistance and decrease in the frequency dependence of compliance, but no change in dynamic compliance. Similar changes were elicited by arachidonic acid infusions. Increases in lung resistance under normal airway tone conditions were attenuated, whereas decreases under enhanced tone conditions induced by arachidonic acid were increased by imidazole, an inhibitor of thromboxane synthesis. These data suggest that dihomo-γ-linoleic acid is converted into products in the monoenoic cyclooxygenase pathway such as PGD₁ and PGF₁(α) which constrict large and small conducting airways as well as certain peripheral areas of the lung. However, when airway smooth muscle tone is elevated with serotonin, the monoenoic precursor is converted into cyclooxygenase products, such as PGE₁, which dilate large and small airways. Our data also suggest that arachidonic acid is converted into cyclooxygenase products which act on similar regions of the lung. It is postulated that the actions of the bisenoic precursor are due, in part, to the formation of thromboxane A₂. This study suggests that dihomo-γ-linolenic acid and arachidonic acid are good substrates for the cyclooxygenase in the feline lung and that responses are dependent on the existing level of bronchomotor tone.