IN-VITRO BRONCHIAL RESPONSIVENESS IN 2 HIGHLY INBRED RAT STRAINS

We investigated methaxcholine (MCh)induced bronchoconstriction in expl anted airways from Fischer and Lewis rats. Lung explants, 0.5- to 1.0- mm thick, were prepared from agarose-inflated lungs of anesthetized 8- to 12-wk-old male rats. After overnight culture, videomicroscopy was used to record baseline images of the individual airways. Dose-respons e curves to MCh were then constructed by repeated administration of MC h; airways were reimaged 10 min after each MCh administration. Airway internal luminal area (A(i)) was measured at successive MCh concentrat ions from 10(-9) to 10(-1) M. In addition to the effective concentrati on leading to 50% of the achieved maximal response, we also determined the effective concentration leading to a 40% reduction in A(i). Both the effective concentration leading to 50% of the achieved maximal res ponse and the concentration leading to a 40% reduction in A(i) were si gnificantly lower among Fischer rat airways (P < 0.05). Airway closure was more common among Fischer rat airways (17%) than among those of L ewis rats (7.5%). Responsiveness of Fischer rat airways was more heter ogeneous than among Lewis airways; a larger number of Fischer rat airw ays exhibited high sensitivity to MCh. There was no relationship betwe en responsiveness and baseline Ai in either strain. In a second experi ment, we measured the rate of contraction of explanted airways from lu ngs inflated to 50, 75, and 100% of total lung capacity. The average r ate of contraction in the first 15 s was higher in Fischer rat airways at each inflation volume. These data indicate that the hyperresponsiv eness of the Fischer rat reflects the responsiveness of individual air ways throughout the airway tree and are consistent with the notion tha t in this model hyperresponsiveness is an intrinsic property of airway smooth muscle.