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 ai rways. However, it is not known whether beta(2)-agonists have this ben eficial effect in airway mucosa that is already inflamed. We evaluated the effects of two inhaled beta(2)-agonists, salbutamol and formotero l, on the histamine-induced bronchoconstriction and plasma extravasati on in the airways of guinea pigs with or without ozone exposure. Total pulmonary resistance (R-L) was measured before and after histamine in halation in anesthetized animals that were pretreated with inhaled sal butamol, formoterol, or saline. Plasma extravasation in the airways wa s 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 increa se in R-L after histamine was greater than that in control animals. Sa lbutamol and formoterol each significantly reduced histamine-induced b ronchoconstriction, even in the ozone-exposed animals. Salbutamol did not affect the histamine-induced plasma extravasation, whereas formote rol reduced the plasma extravasation in the main bronchi, but not in t he trachea, of the animals exposed to ozone. These results suggest tha t the anti-inflammatory properties of formoterol in inflamed airways m ay contribute to the beneficial effects in the treatment of airway inf lammation.