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Airway narrowing in response to different modes of stimuli was measured using a perfused bronchial segment. Acetylcholine, carbachol, histamine, high [K+] and vanadate perfused through the lumen gave small responses as shown by the reduction in flow, but fully constricted the airway when applied to the outside. ACh was 29 times more sensitive on the outside. When the epithelium was removed airway narrowing by these stimuli was increased to equal that on the outside. It was concluded that the role of the epithelia as a barrier is all important. Evidence for an EpDIF released by the epithelium could not be obtained.

To study airway reactivity, flow-resistance to carbachol and histamine was measured in perfused bronchial segments. Small-bore airways were more sensitive, flow was reduced to zero and resistance rose very steeply due to mucosal folding while in large-bore airways maximum flow reduction was 50% and resistance increased sigmoidly. Thus the internal diameter of an airway is a crucial determinant of narrowing.

When bronchial segments were perfused with Krebs solution at a constant pressure (5-6 cmH2O), the resistance rose exponentially with increasing concentrations of either carbachol or histamine in the lumen. The pressure-flow relationship was linear. Histamine and carbachol caused 43 and 47% muscle shortening, respectively, and produced the same maximum effect (Emax) because they both stopped perfusion. In bronchial strips the maximum isometric force or isotonic shortening to carbachol was more than twice that of histamine and the responses showed a plateau. There were no significant differences in sensitivities [negative log of the concentration producing half-maximal response (EC50)] to either carbachol or histamine in the strips (isotonic and isometric) and the segments perfused at constant pressure. When airway segments were perfused at a constant flow, however, responses plateaued and the sensitivities to carbachol and histamine were reduced more than tenfold compared with the strips [4.71 +/- 0.20 and 6.22 +/- 0.08 (SE) for carbachol in segments and isometric strips, respectively, and 3.92 +/- 0.13 and 4.94 +/- 0.11 (SE) for histamine]. We conclude that when segments are perfused at a constant pressure, airway closure occurs before maximal pharmacological activation, as seen in airway strips.