LONG DURATION AND HIGH POTENCY OF ANTIEXUDATIVE EFFECTS OF FORMOTEROL IN GUINEA-PIG TRACHEOBRONCHIAL AIRWAYS

Inflammatory stimulus-induced luminal exudation of plasma proteins is potentially pathogenic in asthma. This study of plasma exudation into tracheobronchial airways examines antiexudative effects (potency and duration of action) of two beta-2-agonists in anesthetized guinea pigs. The exudative response to airway provocations with bradykinin 1.25 x 10(-4) M (5 nmol) was determined in different groups of animals 10, 300, 450, and 600 min, respectively, after the mucosa had been treated topically with salbutamol 10(-6) to 10(-4) M (0.1 to 10 nmol), formoterol 10(-9) to 10(-7) M (0.1 to 10 pmol), or saline (control). Exuded plasma in tracheal lavage liquids was calculated from their contents of the plasma tracer, I-125-albumin, given intravenously 10 min before provocation with bradykinin. Salbutamol (1 and 10 nmol) and formoterol (1 and 10 pmol) promptly inhibited the mucosal exudation (p < 0.001). Propranolol, 0.1 nmol, reduced (p < 0.01) the antiexudative effects of both drugs. Only formoterol (1 and 10 pmol) maintained its effect at 300 min, abating gradually at 450 and 600 min. In a group of sensitized guinea pigs, formoterol (1 and 10 pmol) was demonstrated to inhibit also allergen-induced luminal exudation of plasma (p < 0.001). It is suggested that an antiexudative action may contribute to the long duration of formoterol's antiasthma effect.