Responsiveness of human isolated bronchial segments and its relationship to epithelial loss

1. The responsiveness of human and bovine bronchi was examined by comparing the magnitude of responses to agonists applied to the adventitial (outside) and to the luminal (inside) surfaces. The development of smooth muscle tone was measured as both an increase in pressure in isovolumic bronchial segments and narrowing in perfused segments. 2. In both closed and perfused human segments, ACh added to the adventitial surface produced highly homogeneous responses while responses to ACh added to the luminal side were extremely variable. 3. Histological examination of the human segments showed that they possessed variable degrees of pre-existing epithelial loss from the mucosal circumference, ranging from 0 to 82%. 4. Denuded human isovolumic segments (exhibiting > 30% epithelial loss) were 40 fold more sensitive to ACh inside than intact segments (< 30%). Denuded segments were also equally responsive to KCl inside or outside while KCl inside produced a contraction that was 50% of that to KCl outside in intact segments. 5. A strong and highly significant relationship was determined between the proportion of epithelial loss and both the responsiveness and rate of contraction of human segments to ACh and KCl introduced onto the lumen. No relationship was observed between epithelial denudation and responsiveness or contractility to agonists added to the adventitial surface. 6. Mechanical denudation of the epithelium from bovine segments had no effect on responsiveness to ACh or KCl added to the outside while significantly augmenting the sensitivity to ACh (9 fold) and reactivity to KCl introduced into the lumen to the extent that it became the same as outside.(ABSTRACT TRUNCATED AT 250 WORDS)