title: Effect of nitrite delivered in saliva on postprandial gastro-esophageal function.
abstract: OBJECTIVE
  Acid reflux produces troublesome symptoms (heartburn) and complications including esophagitis, Barrett's esophagus, and adenocarcinoma. Reflux occurs due to excessive and inappropriate relaxation of the lower esophageal sphincter. An important mediator of this is nitric oxide, high concentrations of which are generated within the lumen when swallowed saliva meets gastric acid. Saliva contains nitrite, derived from the enterosalivary recirculation of dietary nitrate, which is reduced to nitric oxide by gastric acid. The aim of this study was to investigate whether salivary nitrite contributes to dysfunction of the lower esophageal sphincter.
  
  
  METHODS
  In 20 volunteers, studies of gastro-esophageal function were performed on four separate days, following consumption of a standardized meal, with saliva nitrite concentrations modified differently each day by intra-oral nitrite infusion.
  
  
  RESULTS
  The infusions produced an appropriate range in saliva nitrite concentrations, from below to well above the physiological range. The standardized meal induced expected physiological changes in gastro-esophageal function confirming the recordings were sensitive and robust. Esophageal acid exposure (primary outcome) was similar on each study day. Secondary outcomes, including number and duration of reflux events, rate of transient lower esophageal sphincter relaxations, lower esophageal sphincter pressure and rate of gastric emptying were also unaffected by variations in saliva nitrite concentration.
  
  
  CONCLUSIONS
  Nitrite in swallowed saliva does not modify gastro-esophageal junction function or predispose to gastro-esophageal reflux. The wide range in saliva nitrite concentrations, the sensitivity of the physiological recordings and the number of subjects studied make it very unlikely that an effect has been missed.
authors.affiliation: Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Seenan
authors.forename: Angela A
authors.initials: AA
authors.lastname: Wirz
authors.forename: Elaine V
authors.initials: EV
authors.lastname: Robertson
authors.forename: Alan T
authors.initials: AT
authors.lastname: Clarke
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Manning
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Kelman
authors.forename: Gerry
authors.initials: G
authors.lastname: Gillen
authors.forename: Stuart
authors.initials: S
authors.lastname: Ballantyne
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Derakhshan
authors.forename: Kenneth E L
authors.initials: KE
authors.lastname: McColl
mesh_terms: D000328:Adult; D049630:Esophageal Sphincter, Lower / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005764:Gastroesophageal Reflux / Q000139:chemically induced; D006801:Humans; D008297:Male; D008365:Manometry; D008875:Middle Aged; D009573:Nitrites / Q000009:adverse effects / Q000494:pharmacology*; D012463:Saliva / Q000737:chemistry*
chemical_list: D009573:Nitrites