Wang C G, Almirall J J, Dolman C S, Dandurand R J, Eidelman D H
Meakins-Christie Laboratories, Royal Victoria Hospital, Montreal General Hospital, Quebec, Canada.
J Appl Physiol (1985). 1997 May;82(5):1445-52. doi: 10.1152/jappl.1997.82.5.1445.
We investigated methacholine (MCh)-induced bronchoconstriction in explanted 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-response curves to MCh were then constructed by repeated administration of MCh; airways were reimaged 10 min after each MCh administration. Airway internal luminal area (Ai) was measured at successive MCh concentrations from 10(-9) to 10(-1) M. In addition to the effective concentration leading to 50% of the achieved maximal response, we also determined the effective concentration leading to a 40% reduction in Ai. Both the effective concentration leading to 50% of the achieved maximal response and the concentration leading to a 40% reduction in Ai were significantly lower among Fischer rat airways (P < 0.05). Airway closure was more common among Fischer rat airways (17%) than among those of Lewis rats (7.5%). Responsiveness of Fischer rat airways was more heterogeneous than among Lewis airways; a larger number of Fischer rat airways exhibited high sensitivity to MCh. There was no relationship between responsiveness and baseline Ai in either strain. In a second experiment, we measured the rate of contraction of explanted airways from lungs inflated to 50, 75, and 100% of total lung capacity. The average rate of contraction in the first 15 s was higher in Fischer rat airways at each inflation volume. These data indicate that the hyperresponsiveness of the Fischer rat reflects the responsiveness of individual airways throughout the airway tree and are consistent with the notion that in this model hyperresponsiveness is an intrinsic property of airway smooth muscle.
我们研究了在费希尔大鼠和刘易斯大鼠的离体气道中，乙酰甲胆碱（MCh）诱导的支气管收缩情况。从8至12周龄麻醉雄性大鼠经琼脂糖充气的肺中制备0.5至1.0毫米厚的肺组织外植体。过夜培养后，使用视频显微镜记录各个气道的基线图像。然后通过重复给予MCh构建MCh的剂量反应曲线；每次给予MCh后10分钟对气道进行重新成像。在10⁻⁹至10⁻¹ M的连续MCh浓度下测量气道内腔面积（Ai）。除了导致达到最大反应50%的有效浓度外，我们还确定了导致Ai减少40%的有效浓度。在费希尔大鼠气道中，导致达到最大反应50%的有效浓度以及导致Ai减少40%的浓度均显著更低（P < 0.05）。气道关闭在费希尔大鼠气道中（17%）比在刘易斯大鼠气道中（7.5%）更常见。费希尔大鼠气道的反应性比刘易斯大鼠气道更具异质性；更多的费希尔大鼠气道对MCh表现出高敏感性。两种品系的反应性与基线Ai之间均无关联。在第二个实验中，我们测量了充气至肺总量50%、75%和100%的肺组织外植体气道的收缩速率。在每个充气量下，费希尔大鼠气道在前15秒的平均收缩速率更高。这些数据表明，费希尔大鼠的高反应性反映了整个气道树中各个气道的反应性，并且与该模型中高反应性是气道平滑肌的固有特性这一观点一致。
