Murine genetic deficiency of neuronal nitric oxide synthase (nNOS‐/‐) and interstitial cells of Cajal (W/Wv): Implications for achalasia?

Medientyp: E-Artikel
Titel: Murine genetic deficiency of neuronal nitric oxide synthase (nNOS‐/‐) and interstitial cells of Cajal (W/Wv): Implications for achalasia?
Beteiligte: Müller, Michaela; Colcuc, Sebastian; Drescher, Daniel G.; Eckardt, Alexander J.; von Pein, Harald; Taube, Christian; Schumacher, Johannes; Gockel, Henning R.; Schimanski, Carl C.; Lang, Hauke; Gockel, Ines
Erschienen: Wiley, 2014
Erschienen in: Journal of Gastroenterology and Hepatology
Sprache: Englisch
DOI: 10.1111/jgh.12600
ISSN: 0815-9319; 1440-1746
Schlagwörter: Gastroenterology ; Hepatology
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Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background and Aim</jats:title><jats:p>Nitric oxide (<jats:styled-content style="fixed-case">NO</jats:styled-content>) is an important inhibitory mediator of esophageal function, and its lack leads to typical features of achalasia. In contrast, the role of intramuscular interstitial cells of <jats:styled-content style="fixed-case">C</jats:styled-content>ajal (<jats:styled-content style="fixed-case">ICC‐IM</jats:styled-content>) and vasoactive intestinal peptide (<jats:styled-content style="fixed-case">VIP</jats:styled-content>) in lower esophageal sphincter (<jats:styled-content style="fixed-case">LES</jats:styled-content>) function is still controversial. Therefore, we examined the function and morphology of the <jats:styled-content style="fixed-case">LES</jats:styled-content> in vivo in <jats:styled-content style="fixed-case">NO</jats:styled-content>‐deficient (<jats:styled-content style="fixed-case">nNOS</jats:styled-content><jats:sup>‐/‐</jats:sup>), <jats:styled-content style="fixed-case">ICC‐IM</jats:styled-content>‐deficient (<jats:styled-content style="fixed-case">W</jats:styled-content>/<jats:styled-content style="fixed-case">W<jats:sup>v</jats:sup></jats:styled-content>)‐, and wild‐type (<jats:styled-content style="fixed-case">WT</jats:styled-content>) mice.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Esophageal manometry was performed with a micro‐sized transducer catheter to quantify <jats:styled-content style="fixed-case">LES</jats:styled-content> pressure, swallow evoked <jats:styled-content style="fixed-case">LES</jats:styled-content> relaxation, and esophageal body motility. The <jats:styled-content style="fixed-case">LES</jats:styled-content> morphology was examined by semiquantitative analysis of the immunoreactivity (reduction grade <jats:styled-content style="fixed-case">I</jats:styled-content>–<jats:styled-content style="fixed-case">IV</jats:styled-content>) of neuronal <jats:styled-content style="fixed-case">NOS</jats:styled-content> (<jats:styled-content style="fixed-case">nNOS</jats:styled-content>), <jats:styled-content style="fixed-case">ICC‐IM</jats:styled-content>, and <jats:styled-content style="fixed-case">VIP</jats:styled-content> and their correlation with esophageal function.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p><jats:styled-content style="fixed-case">nNOS</jats:styled-content><jats:sup>‐/‐</jats:sup> in comparison to <jats:styled-content style="fixed-case">WT</jats:styled-content> mice showed a significantly higher <jats:styled-content style="fixed-case">LES</jats:styled-content> mean resting pressure with an impaired swallow induced relaxation, whereas <jats:styled-content style="fixed-case">W</jats:styled-content>/<jats:styled-content style="fixed-case">W<jats:sup>v</jats:sup></jats:styled-content> mice had a hypotensive <jats:styled-content style="fixed-case">LES</jats:styled-content> with decreased relaxation. <jats:styled-content style="fixed-case">W</jats:styled-content>/<jats:styled-content style="fixed-case">W<jats:sup>v</jats:sup></jats:styled-content> and <jats:styled-content style="fixed-case">nNOS</jats:styled-content><jats:sup>‐/‐</jats:sup> mice demonstrated differing degrees of tubular esophageal dysfunction.</jats:p><jats:p>The reduced immunoreactivity of <jats:styled-content style="fixed-case">nNOS</jats:styled-content> correlated with an increased <jats:styled-content style="fixed-case">LES</jats:styled-content> pressure and decreased <jats:styled-content style="fixed-case">LES</jats:styled-content> relaxation, respectively. <jats:styled-content style="fixed-case">C</jats:styled-content>ajal‐cell reduction correlated with impaired <jats:styled-content style="fixed-case">LES</jats:styled-content> relaxation, whereas <jats:styled-content style="fixed-case">VIP</jats:styled-content> reduction revealed no correlation with esophageal function.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The reduction of <jats:styled-content style="fixed-case">ICC‐IM</jats:styled-content> and <jats:styled-content style="fixed-case">nNOS</jats:styled-content> can cause dysfunction of the <jats:styled-content style="fixed-case">LES</jats:styled-content> and esophageal peristalsis, whereas <jats:styled-content style="fixed-case">VIP</jats:styled-content> reduction seems to have no effect. <jats:styled-content style="fixed-case">ICC‐IM</jats:styled-content> and <jats:styled-content style="fixed-case">nNOS</jats:styled-content> deficiency might be independent relevant causes of esophageal dysfunction similar to that seen in human achalasia.</jats:p></jats:sec>

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