The prostanoids and leukotrienes are extremely potent modulators of airway smooth muscle tone, which play a role, probably to varying degrees, in the bronchospasm of immediate hypersensitivity reactions. There is evidence that the synthesis of these two classes of tissue hormones, both of which derive from arachidonic acid, is significantly different in normal and immunologically-sensitized lungs. Very little is currently known, however, about the patterns of regional synthesis of these arachidonate metabolites in the airways has not been clearly defined. In the proposed studies, a combination of in vivo and in vitro techniques will be utilized to study the synthesis, activity and degradation of prostanoids and leukotrienes in airways at specific levels of the tracheobronchial tree in normal and Ascaris suum-sensitized dogs. Physiologic measurements will include those of pulmonary mechanics, collateral ventilation, pulmonary vascular resistance and shunt fraction. Biochemical studies will involve assay of biosynthetic and degradative enzyme activities in preparations of microsomes from specific airway tissues from normal and sensitized animals. Also, the actions of selected pharmacologtic agents on these systems and on lung function during antigen-induced bronchospasm will be investigated. These studies are designed to improve our understanding of the role of arachidonate metabolites in modulating airway function in the normal and sensitized lung, with the aim of identifying new therapeutic measures for the treatment of allergic lung disease.
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