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

Abstract

BACKGROUND AND AIM:

Nitric oxide (NO) 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 Cajal (ICC-IM) and vasoactive intestinal peptide (VIP) in lower esophageal sphincter (LES) function is still controversial. Therefore, we examined the function and morphology of the LES in vivo in NO-deficient (nNOS(-/-) ), ICC-IM-deficient (W/W(v) )-, and wild-type (WT) mice.

METHODS:

Esophageal manometry was performed with a micro-sized transducer catheter to quantify LES pressure, swallow evoked LES relaxation, and esophageal body motility. The LES morphology was examined by semiquantitative analysis of the immunoreactivity (reduction grade I-IV) of neuronal NOS (nNOS), ICC-IM, and VIP and their correlation with esophageal function.

RESULTS:

nNOS(-/-) in comparison to WT mice showed a significantly higher LES mean resting pressure with an impaired swallow induced relaxation, whereas W/W(v) mice had a hypotensive LES with decreased relaxation. W/W(v) and nNOS(-/-) mice demonstrated differing degrees of tubular esophageal dysfunction. The reduced immunoreactivity of nNOS correlated with an increased LES pressure and decreased LES relaxation, respectively. Cajal-cell reduction correlated with impaired LES relaxation, whereas VIP reduction revealed no correlation with esophageal function.

CONCLUSIONS:

The reduction of ICC-IM and nNOS can cause dysfunction of the LES and esophageal peristalsis, whereas VIP reduction seems to have no effect. ICC-IM and nNOS deficiency might be independent relevant causes of esophageal dysfunction similar to that seen in human achalasia.

• Authors: Michaela Müller, Sebastian Colcuc, Daniel G Drescher, Alexander J Eckardt, Harald von Pein, Christian Taube, Johannes Schumacher, Henning R Gockel, Carl C Schimanski, Hauke Lang, Ines Gockel
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 29 Issue 10 Pg. 1800-7 (Oct 2014) ISSN: 1440-1746 [Electronic] Australia
• PMID: 24720557 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Chemical References

• Nitric Oxide
• Vasoactive Intestinal Peptide
• Nitric Oxide Synthase Type I

Topics

• Animals
• Esophageal Achalasia (etiology, physiopathology)
• Esophageal Sphincter, Lower (physiopathology)
• Female
• Gene Deletion
• Humans
• Interstitial Cells of Cajal (physiology)
• Male
• Manometry
• Mice, Inbred Strains
• Nitric Oxide (physiology)
• Nitric Oxide Synthase Type I (deficiency, genetics)
• Peristalsis
• Vasoactive Intestinal Peptide (physiology)