The effect of verapamil is reduced in isolated airway smooth muscle preparations lacking the epithelium

Abstract

The effect of epithelium removal on the reactivity of rabbit airway smooth muscle to bronchoactive agents and on the effect of verapamil was studied in vitro using preparations from several levels within the respiratory tree, i.e., trachea, primary (1°) and secondary (2°) bronchus. Methacholine contracted tissues from all three levels of airway. Histamine contracted strips from 2° bronchus, had an inconsistent action in strips from 1° bronchus and was without effect in tracheal preparations. K + contracted tissues from the trachea and 1° bronchus, and had a mixed action in 2° bronchial strips. Removal of the epithelial cell layer variably affected the reactivity of the smooth muscle to the three agents studied. In 2° bronchus, epithelium removal potentiated responses to histamine and methacholine. In 1° bronchus, only responses to methacholine were consistently augmented. In tracheal preparations epithelium removal did not alter the reactivity of the tissue to any agent examined. Verapamil (1 μM) attenuated responses to all agents and increased in its potency from tracheal through 1° to 2° bronchial preparations. Following epithelium removal, verapamil was substantially less effective in 2° bronchi, yet its effects were unchanged in the trachea. The results indicate that 1) the epithelial cell layer modulates airway smooth muscle reactivity; this phenomenon is apparently widespread in mammals, 2) the modulatory effect is more prominent in the smaller airways, and 3) the magnitude of the effect of verapamil on airway smooth muscle is, in part, related to the presence of the epithelium.