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 pretreated 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 mmmol/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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Lötvall
J O
JO
Department of Thoracic Medicine, National Heart and Lung Institute and Royal Brompton Hospital, London.
Elwood
W
W
Tokuyama
K
K
Barnes
P J
PJ
Chung
K F
KF
D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects; D005122:Exudates and Transudates / Q000187:drug effects*; D006168:Guinea Pigs; D008168:Lung / Q000098:blood supply; D008833:Microcirculation / Q000187:drug effects; D015260:Neprilysin / Q000037:antagonists & inhibitors; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D010972:Platelet Activating Factor; D015260:Neprilysin