Nitric oxide donor protects against acetic acid-induced gastric ulcer in rats via S-nitrosylation of TRPV1 on vagus nerve

Ting Han,Yan Tang,Liping Gong,Jing Li,Jingxin Li,Bing Xue,Chuanyong Liu,Xiao Yu

doi:10.1038/s41598-017-02275-1

Ting Han, Yan Tang + Show 6 more

Open Access

https://doi.org/10.1038/s41598-017-02275-1

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Journal: Scientific Reports	Publication Date: May 18, 2017
Citations: 15	License type: open-access

Affiliation: Shandong University

Abstract

This study was conducted to investigate the effects of nitric oxide (NO) in acetic acid-induced gastric ulcer of rats and the underlying mechanisms. We found that peritoneal injection of sodium nitroprusside (SNP), a NO donor, decreased the ulcer area, inflammatory cell infiltration and MPO degree in acetic acid-induced gastric ulcer in rats. This effect was abolished by a transient receptor potential vanilloid 1 (TRPV1) antagonist or prior subdiaphragmatic vagotomy. SNP increased the jejunal mesenteric afferent discharge in a dose-depended manner, which was largely diminished by pretreatment of S-nitrosylation blocker N-ethylmaleimide, TRPV1 antagonist capsazepine, genetic deletion of TRPV1, or vagotomy. Whole-cell patch clamp recording showed that SNP depolarized the resting membrane potential of NG neurons, and enhanced capsaicin-induced inward current, which were both blocked by N-ethylmaleimide. Our results suggest that NO donor SNP alleviates acetic acid-induced gastric ulcer in rats via vagus nerve, while S-nitrosylation of TRPV1 may participate in this route. Our findings reveal a new mechanism for vagal afferent activation, and a new potential anti-inflammatory target.

Highlights

MethodsMale Wistar rats (200–270 g) and wild type C57BL6/J mice (6–8 weeks) were procured from the Animal Center of Shandong University
Vagotomy reduced it[21, 22]
We examined the actions of NO on acetic acid-induced gastric ulcer in a rat model, and recorded the mesenteric afferent nerve firing and electrical properties of nodose ganglion neurons to explore the underlying mechanism

Summary

Methods

Male Wistar rats (200–270 g) and wild type C57BL6/J mice (6–8 weeks) were procured from the Animal Center of Shandong University. Male TRPV1-dificient mice (6–8 weeks) were kindly provided by Dr Yu Xiao (Shandong University). The investigation was in accordance with the guide for the care and use of laboratory animals published by the U.S National Institutes of Health (NIH Publication No 85–23). All experiments were approved by the Medical Ethics Committee for Experimental Animals, Shandong University School of Basic Medical Sciences (ECAESDUSM2014056)

Results

Discussion

Conclusion