title: The effects of formoterol on plasma exudation produced by a localized acute inflammatory response to bradykinin in the tracheal mucosa of rats in vivo.
abstract: 1. The effects of formoterol, a beta 2-adrenoceptor agonist, on plasma protein exudation and microvascular permeability induced by topical, i.e. applied onto the tracheal mucosal surface, bradykinin (10 nmol; 20 microM, 5 min, 0.1 ml min-1) were studied in a perfused segment of trachea prepared in situ in anaesthetized rats. 2. Bradykinin increased the amount of plasma (fluorimetric assay for protein) in the perfusate (response; 10.98 +/- 0.357 microliters, n = 69; total increase in plasma over basal during 45 min after start of bradykinin application) and 2 responses at a 90 min interval were reproducible. Carbon labelling was seen in tracheal sections from animals that received i.v. colloidal carbon, indicating that bradykinin caused tracheal microvessels to leak (increase in microvascular permeability). 3. Five minutes after topical formoterol, 5 or 30 nmol (10 or 60 microM perfused for 5 min), the bradykinin response was significantly reduced. The effects of formoterol were not dose-related, i.e. were maximal at 5 nmol. The bradykinin response was at control levels 30 min after 5 nmol formoterol. After 30 nmol formoterol, the response was still reduced 120 min later. The bradykinin response was significantly reduced 60 min after systemic formoterol (i.p., 0.029 to 870 nmol kg-1) and, for 290 nmol kg-1 i.p. formoterol, this reduction was shown to last at least 150 min. 4 The bradykinin response was not prevented by supramaximal doses of topical (30 nmol) or i.p.(870 nmol kg-1) formoterol and carbon-labelled microvessels were seen in tracheal sections from all animals that received formoterol, although these were less in number and less densely labelled than in the absence of formoterol. There was a correlation between the plasma exudation response (ul) and the number of carbon-labelled vessels (Spearman's correlation coefficient 0.415, P<0.001).5 In animals pretreated with propranolol (3 pmol kg-1, i.v.), 29 nmol kg-1 formoterol, i.p., did not reduce the bradykinin response. However, propranolol itself markedly potentiated the bradykinin response which confounded the interpretation of its effects on formoterol.6 The study has shown, in a preparation of rat trachea in situ, that supramaximal doses of the beta2-adrenoceptor agonist, formoterol (a) produced a sustained, but incomplete, inhibition of plasma exudation (induced by topical bradykinin), and (b) did not prevent bradykinin-induced leaky microvessels. The data support the view that, at least in rodent airways, beta2-adrenoceptor agonists attenuate, but do not abolish, the microvascular permeability effects of bradykinin, a putative asthma mediator.
authors.affiliation: Department of Physiology & Pharmacology, University of Queensland, Australia.
authors.forename: S R
authors.initials: SR
authors.lastname: O'Donnell
authors.forename: G P
authors.initials: GP
authors.lastname: Anderson
mesh_terms: D000287:Administration, Topical; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D001920:Bradykinin / Q000633:toxicity*; D002199:Capillary Permeability / Q000187:drug effects*; D002244:Carbon; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004983:Ethanolamines / Q000494:pharmacology*; D005122:Exudates and Transudates / Q000187:drug effects / Q000378:metabolism*; D000068759:Formoterol Fumarate; D007274:Injections, Intraperitoneal; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000098:blood supply* / Q000187:drug effects; D014136:Tracheitis / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D000318:Adrenergic beta-Agonists; D001798:Blood Proteins; D004983:Ethanolamines; D002244:Carbon; D011433:Propranolol; D001920:Bradykinin; D000068759:Formoterol Fumarate