A comparison of in vitro relaxant responses to ipratropium bromide, β-adrenoceptor agonists and theophylline in feline bronchial smooth muscle
2012
Leemans, Jérôme | Kirschvink, Nathalie | Gustin, Pascal
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 (Eₘₐₓ) as the maximal relaxant response and potency (−logEC₅₀) 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. Eₘₐₓ 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 β₂-mimetic dose–response curves. Significant decreases in −logEC₅₀ and Eₘₐₓ 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 β₂-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.
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