Inhaled procaterol inhibits histamine-induced airflow obstruction and microvascular leakage in guinea-pig airways with allergic inflammation

Background: Beta2-adrenoceptor agonists (beta2-agonists) are shown to inhibit airway microvascular leakage in experimental Animals. This effect may change in Animals with chronic airway inflammation.

Objective: We examined whether inhaled beta2-agonists inhibit microvascular leakage in guinea-pig airways with chronic allergic inflammation.

Methods: Three weeks after the sensitization with ovalbumin (OA; 6 mg/mL), each guinea pig was challenged with inhaled OA once a day for 1 or 3 weeks. Control Animals without sensitization with OA also inhaled vehicle for OA (saline) for 3 weeks. One day after the last challenge, different doses of inhaled procaterol (1, 3 or 10 microg/mL) or vehicle was given to Animals for 10 min after an anaesthesia. Fifteen minutes after the end of inhalation, the Animals were given i.v. Evans blue dye (EB dye; 20 mg/kg), a marker of microvascular leakage, and then i.v. histamine (3 or 30 microg/kg) or vehicle. Lung resistance, a parameter of airflow obstruction, was measured for 6 min and the lungs were removed to calculate the amount of extravasated EB dye into the airways.

Results: A significant increase in eosinophil infiltration into the airways was seen in sensitized and challenged Animals compared with control Animals without sensitization. Among Animals receiving antigenic exposure for either 0 (control), 1 or 3 weeks, 10 microg/mL procaterol significantly inhibited 30 microg/kg histamine-induced increase in EB dye extravasation to a similar degree (ranged from 28.7 to 69.8% inhibition) as well as that in lung resistance (more than 90% inhibition in all groups). The minimal dose of procaterol to inhibit 3 microg/kg histamine-induced microvascular leakage was not different between nonsensitized control Animals and those sensitized and challenged for 3 weeks at all airway levels.

Conclusion: Inhaled beta2-adrenoceptor agonists may be also potent in attenuating microvascular leakage even in the airways with chronic allergic inflammation.