Plasma Exudation into Airways Induced by Inhaled Platelet-Activating Factor: Effect of Peptidase Inhibition

1. To evaluate whether endogenous peptide release is involved in the airway responses to inhaled platelet-activating factor, we measured lung resistance and airway microvascular leakage in anaesthetized guinea pigs pre-treated with inhalation of either saline or a combination of the peptidase inhibitors phosphoramidon (0.1 mmol/l: 60 breaths; 7.5 nmol), to inhibit neutral endopeptidase, and captopril (4.6 mmol/l: 60 breaths; 350 nmol), to inhibit angiotensin-converting enzyme. 2. Airway microvascular leakage was determined by the albumin marker Evans Blue dye injected intravenously (20 mg/kg) before platelet-activating factor or sham challenge. 3. Inhaled platelet-activating factor induced a maximum increase in lung resistance (1.43 ± 0.33 cmH2O s−1 ml−1) which was not significantly different after pretreatment with phosphoramidon and captopril (1.44 ± 0.21 cmH2O s−1 ml−1). 4. Inhalation of platelet-activating factor caused a significant increase in extravasated Evans Blue dye at all airway levels, an effect which was not potentiated by peptidase inhibition. Similar results were obtained with dye extravasated into the airway lumen and absorbed by a filter paper placed on the tracheal mucosa. Approximately 11% of the total tracheal dye was found in the lumen. There was a high correlation between tracheal tissue and tracheal lumen Evans Blue dye (r = 0.91; P < 0.001). 5. We found a significantly lower dry to wet weight ratio in proximal intrapulmonary airways of animals exposed to platelet-activating factor, suggesting that platelet-activating factor caused airway oedema at this airway level. 6. Inhaled platelet-activating factor does not induce immediate release of peptides degraded by either neutral endopeptidase or angiotensin-converting enzyme in high enough quantities to cause bronchoconstriction. Inhaled platelet-activating factor may cause airway narrowing in guinea pigs largely due to plasma exudation into the airway wall and lumen.