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Medientyp:
E-Artikel
Titel:
Characterization of airway and vascular responses in murine lungs
Beteiligte:
Held, Heinz‐Dieter;
Martin, Christian;
Uhlig, Stefan
Erschienen:
Wiley, 1999
Erschienen in:British Journal of Pharmacology
Sprache:
Englisch
DOI:
10.1038/sj.bjp.0702394
ISSN:
0007-1188;
1476-5381
Entstehung:
Anmerkungen:
Beschreibung:
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<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>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 (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 (<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>U46619, 0.05<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<Mch <U46619<ET‐1. The reagibility of the murine pulmonary vasculature is serotonin<LTC<jats:sub>4</jats:sub>∼PAF <U46619<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>