INHALED PROCATEROL INHIBITS HISTAMINE-INDUCED AIR-FLOW OBSTRUCTION AND MICROVASCULAR LEAKAGE IN GUINEA-PIG AIRWAYS WITH ALLERGIC INFLAMMATION

Background beta(2)-adrenoceptor agonists (beta(2)-agonists) are shown to inhibit airway microvascular leakage in experimental animals. This effect may change in animals with chronic airway inflammation. Objecti ve We examined whether inhaled beta(2)-agonists inhibit microvascular leakage in guinea-pig airways with chronic allergic inflammation. Meth ods Three weeks after the sensitization with ovalbumin (OA; 6 mg/mL), each guineapig was challenged with inhaled OA once a day for 1 or 3 we eks. Control animals without sensitization with OA also inhaled vehicl e for OA (saline) for 3 weeks. One day after the last challenge, diffe rent doses of inhaled procaterol (1, 3 or 10 mu g/mL) or vehicle was g iven 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. hist amine (3 or 30 mu g/kg) or vehicle. Lung resistance, a parameter of ai rflow obstruction, was measured for 6 min and the lungs were removed t o calculate the amount of extravasated EB dye into the airways. Result s A significant increase in eosinophil infiltration into the airways w as seen in sensitized and challenged animals compared with control ani mals without sensitization. Among animals receiving antigenic exposure for either 0 (control), 1 or 3 weeks, 10 mu g/mL procaterol significa ntly inhibited 30 mu g/kg histamine-induced increase in EB dye extrava sation to a similar degree (ranged from 28.7 to 69.8% inhibition) as w ell as that in lung resistance (more than 90% inhibition in all groups ). The minimal dose of procaterol to inhibit 3 mu g/kg histamine-induc ed microvascular leakage was not different between nonsensitized contr ol animals and those sensitized and challenged for 3 weeks at all airw ay levels. Conclusion Inhaled beta(2)-adrenoceptor agonists may be als o potent in attenuating microvascular leakage even in the airways with chronic allergic inflammation.