Characterization of airway and vascular responses in murine lungs

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Abstract
We characterized the responses of murine airways and pulmonary vessels to a variety of endogenous mediators in the isolated perfused and ventilated mouse lung (IPL) and compared them with those in precision‐cut lung slices. Airways: The EC50 (μM) for contractions of airways in IPL/slices was methacholine (Mch), 6.1/1.5>serotonin, 0.7/2.0>U46619 (TP‐receptor agonist), 0.1/0.06>endothelin‐1, 0.1/0.05. In the IPL, maximum increase in airway resistance (RL) was 0.6, 0.4, 0.8 and 11 cmH2O s ml−1, respectively. Adenosine (1 mM), bombesin (100 μM), histamine (10 mM), LTC4 (1 μM), PAF (0.25 μM) and substance P (100 μM) had only weak effects (L. Vessels: The EC50 (μM) for vasoconstriction in the IPL was LTC4, 0.06>U46619, 0.052O, respectively. At 250 nM, the activity of PAF was comparable to that of LTC4. At 100 μM only, substance P caused a largely variable increase in PAP. Serotonin, adenosine, bombesin, histamine and Mch had no or only very small effects on PAP. Hyperresponsiveness: In both the IPL and slices, U46619 in subthreshold concentrations (10 nM) reduced the EC50 to 0.6 μM. In the IPL, U46619 raised the maximum airway response to Mch 5 fold and the maximum PAF‐induced vasoconstriction 4 fold. Conclusion: Murine precision‐cut lung slices maintain important characteristics of the whole organ. The maximum reagibility of murine airways to endogenous mediators is serotonin4∼PAF British Journal of Pharmacology (1999) 126, 1191–1199; doi:10.1038/sj.bjp.0702394

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