Effects of bronchoconstrictors and bronchodilators on a novel human small airway preparation

Human lung bronchiolar segments (about 2 mm long and with a diameter of 0.6-1.5 mm) were dissected and circular muscle tension recorded. Airways were identified by histology and in some preparations by relaxant responses to noradrenaline (0.1-10 microM). Adenosine (1-100 microM) produced only very weak contractions, whereas carbachol (EC50 = 0.40 microM), histamine (EC50 = 0.63 microM), prostaglandin D2 (EC50 = 0.50 microM), substance P (EC50 = 4.6 microM) and ATP (1-100 microM) produced much greater ones. The contractions generally developed rapidly and were stable. The mean maximum increase in tension achieved with the most efficient constrictor, carbachol, was 0.5 g. ATP was the least efficient producing only about 40% of carbachol's maximum. Terbutaline, theophylline and enprofylline relaxed carbachol (2.0 microM = EC70)-contracted preparations. Terbutaline (3-3000 nM) relaxed 4 out of 11 bronchioles. Theophylline (10-4000 microM) and enprofylline (1-400 microM) consistently relaxed the bronchiolar preparations including those exhibiting little responsiveness to the beta 2-adrenoceptor agonist. Since enprofylline (which does not block adenosine receptors) was a five times more potent relaxant than theophylline and since adenosine produced only weak contractions, antagonism of adenosine receptors is probably not involved in relaxation of the small airways. It is suggested that the present data, which apparently differ from those obtained with lung parenchymal strips, are of relevance for human small airways responsiveness.