Clinical & Experimental Allergy

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

Authors


Dr Tokuyama Department of Paediatrics, Gunma University School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma 371, Japan.

Abstract

Background

β2-adrenoceptor agonists (β2-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 β2-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 μg/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 μg/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 μg/mL procaterol significantly inhibited 30 μg/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 μg/kg histamine-induced microvascular leakage was not different between non-sensitized control animals and those sensitized and challenged for 3 weeks at all airway levels.

Conclusion

Inhaled β2-adrenoceptor agonists may be also potent in attenuating microvascular leakage even in the airways with chronic allergic inflammation.

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