Effect of beta 2-agonists on histamine-induced airway microvascular leakage in ozone-exposed guinea pigs

beta 2-adrenergic agonists exhibit antipermeability effects in the airways. However, it is not known whether beta 2-agonists have this beneficial effect in airway mucosa that is already inflamed. We evaluated the effects of two inhaled beta 2-agonists, salbutamol and formoterol, on the histamine-induced bronchoconstriction and plasma extravasation in the airways of guinea pigs with or without ozone exposure. Total pulmonary resistance (RL) was measured before and after histamine inhalation in anesthetized animals that were pretreated with inhaled salbutamol, formoterol, or saline. Plasma extravasation in the airways was measured using Evans blue dye. In the control animals not exposed to ozone, salbutamol and formoterol each significantly reduced both the histamine-induced bronchoconstriction and the plasma extravasation in the trachea and main bronchi. In the ozone-exposed animals, the increase in RL after histamine was greater than that in control animals. Salbutamol and formoterol each significantly reduced histamine-induced bronchoconstriction, even in the ozone-exposed animals. Salbutamol did not affect the histamine-induced plasma extravasation, whereas formoterol reduced the plasma extravasation in the main bronchi, but not in the trachea, of the animals exposed to ozone. These results suggest that the anti-inflammatory properties of formoterol in inflamed airways may contribute to the beneficial effects in the treatment of airway inflammation.