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Held, Heinz‐Dieter; Martin, Christian; Uhlig, Stefan

Characterization of airway and vascular responses in murine lungs

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  • Media type: E-Article
  • Title: Characterization of airway and vascular responses in murine lungs
  • Contributor: Held, Heinz‐Dieter; Martin, Christian; Uhlig, Stefan
  • imprint: Wiley, 1999
  • Published in: British Journal of Pharmacology
  • Language: English
  • DOI: 10.1038/sj.bjp.0702394
  • ISSN: 0007-1188; 1476-5381
  • Origination:
  • Footnote:
  • Description: <jats:p> <jats:list list-type="explicit-label"> <jats:list-item><jats:p>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.</jats:p></jats:list-item> <jats:list-item><jats:p>Airways: The EC<jats:sub>50</jats:sub> (μ<jats:sc>M</jats:sc>) for contractions of airways in IPL/slices was methacholine (Mch), 6.1/1.5&gt;serotonin, 0.7/2.0&gt;U46619 (TP‐receptor agonist), 0.1/0.06&gt;endothelin‐1, 0.1/0.05. In the IPL, maximum increase in airway resistance (R<jats:sub>L</jats:sub>) was 0.6, 0.4, 0.8 and 11 cmH<jats:sub>2</jats:sub>O s ml<jats:sup>−1</jats:sup>, respectively. Adenosine (1 m<jats:sc>M</jats:sc>), bombesin (100 μ<jats:sc>M</jats:sc>), histamine (10 m<jats:sc>M</jats:sc>), LTC<jats:sub>4</jats:sub> (1 μ<jats:sc>M</jats:sc>), PAF (0.25 μ<jats:sc>M</jats:sc>) and substance P (100 μ<jats:sc>M</jats:sc>) had only weak effects (&lt;5% of Mch) on R<jats:sub>L</jats:sub>.</jats:p></jats:list-item> <jats:list-item><jats:p>Vessels: The EC<jats:sub>50</jats:sub> (μ<jats:sc>M</jats:sc>) for vasoconstriction in the IPL was LTC<jats:sub>4</jats:sub>, 0.06&gt;U46619, 0.05&lt;endothelin‐1, 0.02. The maximum increase in pulmonary artery pressure (PAP) was 11, 41 and 48 cmH<jats:sub>2</jats:sub>O, respectively. At 250 n<jats:sc>M</jats:sc>, the activity of PAF was comparable to that of LTC<jats:sub>4</jats:sub>. At 100 μ<jats:sc>M</jats:sc> 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.</jats:p></jats:list-item> <jats:list-item><jats:p>Hyperresponsiveness: In both the IPL and slices, U46619 in subthreshold concentrations (10 n<jats:sc>M</jats:sc>) reduced the EC<jats:sub>50</jats:sub> to 0.6 μ<jats:sc>M</jats:sc>. In the IPL, U46619 raised the maximum airway response to Mch 5 fold and the maximum PAF‐induced vasoconstriction 4 fold.</jats:p></jats:list-item> <jats:list-item><jats:p>Conclusion: Murine precision‐cut lung slices maintain important characteristics of the whole organ. The maximum reagibility of murine airways to endogenous mediators is serotonin&lt;Mch &lt;U46619&lt;ET‐1. The reagibility of the murine pulmonary vasculature is serotonin&lt;LTC<jats:sub>4</jats:sub>∼PAF &lt;U46619&lt;ET‐1. The airway and vessel hyperreactivity induced by U46619 raises the possibility that thromboxane contributes directly to airway hyperresponsiveness in various experimental and clinical settings.</jats:p></jats:list-item> </jats:list> </jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (1999) <jats:bold>126</jats:bold>, 1191–1199; doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0702394">10.1038/sj.bjp.0702394</jats:ext-link></jats:p>
  • Access State: Open Access