A comparison of in vitro relaxant responses to ipratropium bromide, β-adrenoceptor agonists and theophylline in feline bronchial smooth muscle

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 (−log EC50) 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 −log EC50 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.