THE INTEGRITY OF THE EPITHELIUM IS A MAJOR DETERMINANT OF THE RESPONSIVENESS OF THE DOG BRONCHIAL SEGMENT TO MUCOSAL PROVOCATION

The intact bronchial segment of the dog was used to investigate the role of the epithelium in modulating bronchial responsiveness: firstly, because it retains many of the properties of the airway wall including the separation of the mucosal and adventitial surfaces; and secondly, because airway tissue from dogs has been principally used in advancing evidence for epithelial relaxant substances. The development of tone by the airway smooth muscle was measured as an increase in luminal pressure of the isovolumic segment. Cholinergic excitatory and sympathetic inhibitory responses were obtained to electrical field stimulation. Responses to acetylcholine (ACh), carbachol, depolarizing K+ solution and vanadate (VO3—) applied to the mucosal surface were greatly attenuated both in sensitivity and reactivity compared with their effect on the adventitial surface. Mechanical removal of the epithelium greatly augmented these responses to agents in the lumen (ACh sensitivity increased 100-fold) to equal those by adventitial stimulation. The latter were unaffected by epithelial removal. No functional evidence for epithelial-derived inhibitory factors could be demonstrated. It is concluded that the impermeable nature of the epithelium acts as a barrier to diffusion of hydrophilic and charged molecules thereby producing large concentration gradients across the airway wall. A breach in the integrity of the epithelium enables molecules to gain access to the smooth muscle. © 1993 Academic Press.