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, 125I-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 less than 0.001). Propranolol, 0.1 nmol, reduced (p less than 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 less than 0.001). It is suggested that an antiexudative action may contribute to the long duration of formoterol's antiasthma effect.
Department of Pharmacology, Astra Draco, Lund, Sweden.
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D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000485:Allergens; D000818:Animals; D001920:Bradykinin; D001980:Bronchi / Q000187:drug effects*; D001985:Bronchial Provocation Tests; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology*; D005122:Exudates and Transudates / Q000187:drug effects*; D000068759:Formoterol Fumarate; D006168:Guinea Pigs; D008297:Male; D013997:Time Factors; D014132:Trachea / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D000485:Allergens; D001993:Bronchodilator Agents; D004983:Ethanolamines; D000420:Albuterol; D001920:Bradykinin; D000068759:Formoterol Fumarate