Because both bradykinin and tachykinins have a potent inflammatory action, these molecules may be involved in the late allergic response. The role of these molecules in airway microvascular permeability during the late allergic response in sensitized guinea-pigs was investigated. Three weeks after ovalbumin sensitization, the animals were pretreated with bradykinin B2 receptor antagonist HOE 140, neurokinin 1 receptor antagonist CP 96,345 or vehicle, 30 min before the ovalbumin inhalation challenge. The occurrence of the late allergic response was determined by a two-fold increase in the transpulmonary pressure from the baseline values. The microvascular permeability in the trachea was assessed by an index defined as the ratio of the area of vasculature labelled by Monastral blue dye (area density %). Significant microvascular permeability and eosinophil accumulation were observed during the late allergic response. Both the bradykinin and substance P concentrations in the bronchoalveolar lavage fluid were increased during the late allergic response. Pretreatment with HOE 140 suppressed the substance P elevation. Both HOE 140 and CP 96,345 also inhibited the airway microvascular permeability during the late allergic response without affecting the eosinophil accumulation in the airways. These findings suggest that bradykinin-mediated sensory nerve activation may play a role in microvascular permeability during the late allergic response in guinea-pigs.
- Airway inflammation
- Substance P