Increase of n-NOS and i-NOS in Rat Colon After Sacral Neuromodulation

Neuromodulation. 2017 Dec;20(8):761-766. doi: 10.1111/ner.12644. Epub 2017 Aug 24.

Abstract

Objective: Sacral neuromodulation (SNM) is proposed to treat different anorectal dysfunctions but its mechanism of action is not yet known. Our previous study demonstrated how SNM can significantly increase neuronal nitric oxide synthase NOS (n-NOS) and inducible NOS (i-NOS) expression in the anus and rectum of rats. There are no reports regarding the relation between SNM and NOS in colonic cells: our aim was to assess NOS expression in colonic rat model after SNM.

Materials and methods: Twenty-six female Sprangue-Dawley rats were considered: group I, normal control rats; group II, sham treatment rats, in whom electrodes for electrical stimulation were placed in S1 foramen bilaterally and left in place, without performing neuromodulation; group III, rats in whom SNM was performed. After 14 days, the rats were sacrificed and we evaluated n-NOS and i-NOS in colonic specimens by immunohistochemistry and Western Blot analysis.

Results: Western Blot analysis showed that levels of n-NOS and i-NOS were higher in colon of the III group rats respect to the others; in particular, immunohistochemistry revealed that, after neuromodulation, n-NOS expression in the muscle cells and i-NOS expression in glandular epithelium and nervous cells were highly represented (p < 0.05).

Conclusion: Our study showed that in colon, SNM is able to influence NO synthesis, activating n-NOS expression in muscle cells and i-NOS expression in glandular epithelium and nervous cells. Our study showed a complex colonic response to SNM. This experimental model could be applied to better understand the mechanism of action of SNM in bowel dysfunction.

Keywords: Animal model; bowel dysfunction; colon; neuromodulation; nitric oxide.

MeSH terms

  • Animals
  • Colon / chemistry
  • Colon / enzymology*
  • Electric Stimulation / methods
  • Female
  • Nitric Oxide Synthase Type I / analysis
  • Nitric Oxide Synthase Type I / biosynthesis*
  • Nitric Oxide Synthase Type II / analysis
  • Nitric Oxide Synthase Type II / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Sacrum / chemistry
  • Sacrum / enzymology*

Substances

  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat