Gao, Yuansheng

The present study was designed to determine the role of the respiratory epithelium as a diffusion barrier and a modulator of the responsiveness of airway smooth muscle to bronchoactive agents. Segments of canine bronchi, with or without epithelium, were suspended in organ chambers and perfused intraluminally. The isometric tension was recorded. Acetylcholine, given intraluminally, induced significantly smaller contractions in bronchi with than in bronchi without epithelium. When this agonist was given extraluminally, no difference in contractions was noted between the tissues. In the presence of acetylcholine and phentolamine, norepinephrine, given either intra- or extraluminally, induced significantly larger relaxations in bronchi with than in bronchi without epithelium. High potassium given intraluminally induced contractions only in bronchi without epithelium; however, in the presence of ouabain, both tissues contracted similarly. When high potassium was given extraluminally, no difference in contraction between tissues with and without epithelium was noted. When [3H]acetylcholine and [3H]norepinephrine were perfused intraluminally, the accumulation of 3H radioactivity in the extraluminal solutions was significantly less in bronchi with than in bronchi without epithelium. These observations suggest that the epithelium acts as both a diffusion barrier and a modulator of the responses of canine airways to bronchoactive agents.

Experiments were designed to determine whether the airway epithelium affects the membrane potential of the underlying smooth muscle. The effect of epithelium removal (by gentle rubbing) on the responsiveness of isolated canine bronchi was studied. Simultaneous recordings of mechanical and electrical activity were made in paired circumferential strips (with and without epithelium) of third-order bronchi. Changes in tension were recorded with a force transducer, and changes in membrane potential were measured with a microelectrode. The cell membrane potential and resting tension of the bronchial smooth muscle were stable over a 150-min period and were not affected by removal of the epithelium. In the presence of antagonists at muscarinic and adrenergic receptors, the resting tension and membrane potential were comparable in preparations with and without epithelium. By contrast, the anticholinesterase, echothiophate, caused depolarization in bronchi without epithelium. Exposure to high potassium induced similar levels of depolarization and contraction in tissues with and without epithelium. No significant differences in threshold for depolarization or for mechanical activation in the membrane potential-tension relationship were noted in the presence or absence of epithelium. In the presence of echothiophate, removal of the epithelium augmented the contraction of the bronchi to acetylcholine; the depolarization of the cell membrane induced by the cholinergic transmitter was significantly larger than in control tissues, even when matched contractions were compared. These observations indicate that the respiratory epithelium generates an inhibitory substance that dampens depolarization and contraction of bronchial smooth muscle caused by acetylcholine.