title: A comparison of in vitro relaxant responses to ipratropium bromide, β-adrenoceptor agonists and theophylline in feline bronchial smooth muscle.
abstract: This study compares the potency and efficacy of different relaxant drugs including anticholinergic, β-adrenergic and methylxanthine agents on acetylcholine-contracted feline bronchi, and investigates the influence of the initial muscarinic-induced tone on bronchodilator response. Feline bronchi were removed from euthanased client-owned cats and were contracted with acetylcholine to cause either 40% or 80% of the acetylcholine maximal contraction. The efficacy and potency of bronchodilating drugs were obtained from cumulative dose-response curves with efficacy (E(max)) as the maximal relaxant response and potency (-logEC(50)) as the logarithm of the concentration of drug inducing 50% of maximal relaxation. Under low contractile tone (40%), all bronchodilators relaxed feline bronchi in a concentration-dependent manner with the following rank order of potency: formoterol>ipratropium bromide>fenoterol>isoprenaline>salbutamol≥salmeterol>theophylline. E(max) values ranged from 80% to 100% depending on the tested drug. Constriction of feline bronchi with high-dose acetylcholine (80%) caused a rightward and downward shift of the β(2)-mimetic dose-response curves. Significant decreases in -logEC(50) and E(max) values were reported for salbutamol, formoterol and salmeterol. This study provides evidence that existing classes of bronchodilators produce effective relaxation of acetylcholine-contracted feline bronchi and that airway responsiveness to β(2)-stimulants is dependent on the magnitude of the initial muscarinic-induced tone. The clinical relevance of these in vitro findings has yet to be explored in clinical trials.
authors.affiliation: Section of Pharmacology, Pharmacotherapy and Toxicology, Department of Functional Sciences B41, Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium. jerome.leemans@gmail.com
authors.forename: Jérôme
authors.initials: J
authors.lastname: Leemans
authors.forename: Nathalie
authors.initials: N
authors.lastname: Kirschvink
authors.forename: Pascal
authors.initials: P
authors.lastname: Gustin
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002415:Cats / Q000502:physiology*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009241:Ipratropium / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects*; D013806:Theophylline / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D013806:Theophylline; D009241:Ipratropium