Iijima, K.; Grant, J.; McElroy, K.; Anderson, S.; Fyfe, V.; Paterson, S.; Preston, T.; McColl, K.E.L.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA41
Academic Journal
High concentrations of nitric oxide are generated at the gastro-oesophageal (GO) junction due to the reduction of salivary nitrite to nitric oxide by acidic gastric juice containing ascorbic acid. Salivary nitrite is derived from the enterosalivary recirculation of dietary nitrate. Aims: To determine whether nitric oxide generated in the above way will exert nitrosative stress on the adjacent epithelium. Methods: A benchtop model was constructed reproducing the chemistry occurring at the GO junction and incorporating an epithelial compartment maintained at pH 7.4 separated from the lumen by a thin hydrophobic barrier. The secondary amine morpholine was added to each compartment and N-nitrosomorpholine formation at 15 min measured. Results: Adding 100µM nitrite to the acidic (pH 1.5) luminal compartment in the absence of ascorbic acid generated 6.2±2.0 (mean±SE) N-nitrosomorpholine in that compartment and 2.2±0.1 µM in the epithelial compartment. When 100µM nitrite was added to the acidic luminal compartment (pH 1.5) containing ascorbic acid, all the nitrite was immediately converted to nitric oxide and no N-nitrosomorpholine was formed within that compartment. However, the nitric oxide rapidly diffused into the adjacent epithelial compartment (pH 7.4) where it generated very high concentrations of N-nitrosomorpholine (137±5.6µM). The addition of ascorbic acid or glutathione to the epithelial compartment only reduced this nitric oxide induced nitrosation within the epithelial compartment by 40%. Conclusion: Ascorbic acid in gastric juice prevents acid-catalysed nitrosation within the gastric lumen. However, in doing so it generates nitric oxide which exerts a far higher nitrosative stress on the adjacent epithelium. This mechanism may be relevant to the aetiology of mutagenesis at the GO junction.


Related Articles

  • The Acid Pocket: Rediscovery of an Old Concept. Trang, Tony; Graham, David Y // American Journal of Gastroenterology;Jan2014, Vol. 109 Issue 1, p136 

    A letter to the editor is presented in response to the article "Unbuffered highly acidic gastric juices exist at the gastroesophageal junction after a meal" by J. Fletcher and colleagues in the 2001 issue of the periodical.

  • Expression of inducible nitric oxide synthase in the lower esophageal sphincter of the endotoxemic opossum. Park, Hyojin; Clark, Eugene; Cullen, Joseph J.; Koland, John G; Myong Soo Kim; Conklin, Jeffrey L. // Journal of Gastroenterology;2002, Vol. 37 Issue 12, p1000 

    Background. Endotoxin modulates esophageal motor function by increasing nitric oxide (NO) production. The aims of this study were to examine inducible nitric oxide synthase (iNOS) induction in the lower esophageal sphincter (LES) of endotoxemic opossums and to investigate the effects of...

  • The role of inducible nitric oxide synthase in the relaxation of lower esophageal sphincter in septic state. Iijima, Katsunori; Ohara, Shuich; Shimosegawa, Tooru // Journal of Gastroenterology;2002, Vol. 37 Issue 12, p1090 

    Editorial. Discusses the role of inducible nitric oxide synthase in the relaxation of lower esophageal sphincter in septic state. Two major classes of nitric oxide synthase; Association of endotoxemia and sepsis with clinical symptoms of abnormal motility of the gastrointestinal tract;...

  • Nitric Oxide -- A Major Player in Esophageal Motility. Zayat, Estephan N.; Schuster, Marvin M.; Johnson, David // American Journal of Gastroenterology;Jun2000, Vol. 95 Issue 6, p1584 

    This study evaluated the effect of an infusion of L-NMMA (N-monomethyl-L-Arginine), an inhibitor of nitric oxide synthesis, on 1) esophageal body and lower esophageal sphincter (LES) motility, and 2) gastric distention-triggered transient LES relaxation (TLESR). Thirteen healthy male subjects...

  • Association Between Achalasia and Nitric Oxide Synthase Gene Polymorphisms. Mearin, Fermín; García-González, María-Asunción; Strunk, Michael; Zárate, Natalia; Malagelada, Juán-Ramón; Lanas, Angel // American Journal of Gastroenterology;Sep2006, Vol. 101 Issue 9, p1979 

    BACKGROUND: Our group previously reported the absence of nitric oxide synthase (NOS) in the gastroesophageal junction of patients with achalasia. NOS exists in three distinct isoforms: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible isoform (iNOS). Some studies have shown that NO...

  • The Effect of Sildenafil on Lower Esophageal Sphincter and Body Motility in Normal Male Adults. Rhee, Poong-Lyul; Hyun, Jae Geun; Lee, Jun Haeng; Young-Ho Kim; Hee Jung Son; Kim, Jae J.; Seung Woon Paik; Rhee, Jong Chul; Kyoo Wan Choi // American Journal of Gastroenterology;Dec2001, Vol. 96 Issue 12, p3251 

    OBJECTIVE: Sildenafil relaxes smooth muscle by blocking type 5 phosphodiesterase, which destroys nitric oxide-stimulated cyclic guanosine monophosphate. The aim of this study is to investigate the change of lower esophageal sphincter (LES) and body motility with the lapse of time after...

  • Helicobacter pylori and the Efficacy of Omeprazole Therapy for Gastroesophageal Reflux Disease. Schetik, B. E.; Kuipers, E. J.; Klinkenberg-Knol, E. C.; Eskes, S. A.; Meuwissen, S. G. M. // American Journal of Gastroenterology;Apr1999, Vol. 94 Issue 4, p884 

    OBJECTIVE: Helicobacter pylori infection may affect gastric acid output and intragastric pH. In patients with an insufficient lower esophageal sphincter, this effect may theoretically influence the severity of reflux disease, as well as the efficacy of acid suppressive therapy. To evaluate...

  • Endoscopic treatment modalities for gastroesophageal reflux disease. Lutfi, R. E.; Torquati, A.; Richards, W. O. // Surgical Endoscopy;Sep2004, Vol. 18 Issue 9, p1299 

    A debate has been going for decades between surgeons and gastroenterologists about the treatment of choice for gastroesophageal reflux disease (GERD). The lower esophageal sphincter (LES) has been historically far from the reach of gastroenterologists, who adopted the symptomatic treatment as...

  • Thoraco-abdominal pressure gradients during the phases of respiration contribute to gastroesophageal reflux disease. Ayazi, Shahin; DeMeester, Steven; Hsieh, Chih-Cheng; Zehetner, Joerg; Sharma, Gaurav; Grant, Kimberly; Oh, Daniel; Lipham, John; Hagen, Jeffrey; DeMeester, Tom; DeMeester, Steven R; Grant, Kimberly S; Oh, Daniel S; Lipham, John C; Hagen, Jeffrey A; DeMeester, Tom R // Digestive Diseases & Sciences;Jun2011, Vol. 56 Issue 6, p1718 

    Background and Aims: Exaggerated pressure fluctuation between the thorax and abdomen during exercise or with pulmonary disease may challenge the gastroesophageal barrier and allow reflux of gastric juice into the esophagus. The aim of this study was to investigate the pressure...


Read the Article


Sign out of this library

Other Topics