title: Inhaled formoterol inhibits histamine-induced airflow obstruction and airway microvascular leakage.
abstract: We studied the effects of inhaled formoterol (0.75 mg/ml, 60 breaths = 26 micrograms), a long-acting beta 2-adrenoceptor agonist, or of the more short-acting drug, salbutamol (25 mg/ml, 60 breaths = 875 micrograms), on acute airflow obstruction and airway microvascular leakage (MVL) induced by inhaled histamine in anesthetized guinea pigs. Lung resistance (RL) and its recovery following hyperinflation (recovery RL) were measured for 6 min after histamine (1 or 2 mg/ml, 30 breaths) in animals pretreated with either inhaled beta 2-adrenoceptor agonist or inhaled saline (0.9%, 60 breaths). MVL was measured by determining the amount of extravasated Evans blue dye at various airway levels. Histamine increased RL dose dependently with a mean peak RL (+/- S.E.M.) of 13.1 +/- 2.41 cmH2O/ml per s after 2 mg/ml of histamine. Both formoterol and salbutamol significantly inhibited both peak and recovery RL and MVL to a similar degree. There was a significant correlation between the degree of extravasated dye and both peak and recovery RL, suggesting that MVL partly contributes to histamine-induced airflow obstruction. Formoterol is approximately 35 times more potent than salbutamol to inhibit both MVL and airflow obstruction induced by histamine aerosol.
authors.affiliation: Department of Thoracic Medicine, National Heart and Lung Institute and Brompton Hospital, London, U.K.
authors.forename: K
authors.initials: K
authors.lastname: Tokuyama
authors.forename: J O
authors.initials: JO
authors.lastname: Lötvall
authors.forename: C G
authors.initials: CG
authors.lastname: Löfdahl
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: K F
authors.initials: KF
authors.lastname: Chung
mesh_terms: D000280:Administration, Inhalation; D000402:Airway Obstruction / Q000139:chemically induced / Q000517:prevention & control*; D000403:Airway Resistance / Q000187:drug effects; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D005070:Evans Blue; D005260:Female; D000068759:Formoterol Fumarate; D006168:Guinea Pigs; D006632:Histamine; D006633:Histamine Antagonists; D008168:Lung / Q000503:physiopathology; D008833:Microcirculation / Q000187:drug effects
chemical_list: D001993:Bronchodilator Agents; D004983:Ethanolamines; D006633:Histamine Antagonists; D005070:Evans Blue; D006632:Histamine; D000420:Albuterol; D000068759:Formoterol Fumarate