title: Ethyl nitrite is produced in the human stomach from dietary nitrate and ethanol, releasing nitric oxide at physiological pH: potential impact on gastric motility.
abstract: BACKGROUND
  Nitric oxide ((∙)NO), a ubiquitous molecule involved in a plethora of signaling pathways, is produced from dietary nitrate in the gut through the so-called nitrate-nitrite-NO pathway. In the stomach, nitrite derived from dietary nitrate triggers a network of chemical reactions targeting endogenous and exogenous biomolecules, thereby producing new compounds with physiological activity.
  
  
  OBJECTIVE
  The aim of this study was to ascertain whether compounds with physiological relevance are produced in the stomach upon consumption of nitrate- and ethanol-rich foods.
  
  
  METHODS
  Human volunteers consumed a serving of lettuce (source of nitrate) and alcoholic beverages (source of ethanol). After 15 min, samples of the gastric headspace were collected and ethyl nitrite was identified by GC-MS. Wistar rats were used to study the impact of ethyl nitrite on gastric smooth muscle relaxation at physiological pH.
  
  
  RESULTS
  Nitrogen oxides, produced from nitrite in the stomach, induce nitrosation of ethanol from alcoholic beverages in the human stomach yielding ethyl nitrite. Ethyl nitrite, a potent vasodilator, is produced in vivo upon the consumption of lettuce with either red wine or whisky. Moreover, at physiological pH, ethyl nitrite induces gastric smooth muscle relaxation through a cGMP-dependent pathway. Overall, these results suggest that ethyl nitrite is produced in the gastric lumen and releases (∙)NO at physiological pH, which ultimately may have an impact on gastric motility. Systemic effects may also be expected if ethyl nitrite diffuses through the gastric mucosa reaching blood vessels, therefore operating as a (∙)NO carrier throughout the body.
  
  
  CONCLUSIONS
  These data pinpoint posttranslational modifications as an underappreciated mechanism for the production of novel molecules with physiological impact locally in the gut and highlight the notion that diet may fuel compounds with the potential to modulate gastrointestinal welfare.
authors: Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, 3000-548 Coimbra, Portugal.
authors: Bárbara S
authors: BS
authors: Rocha
authors: Department of Health Sciences, University of Aveiro, Aveiro, Portugal.
authors: Bruno
authors: B
authors: Gago
authors: Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, 3000-548 Coimbra, Portugal.
authors: Rui M
authors: RM
authors: Barbosa
authors: Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, 3000-548 Coimbra, Portugal.
authors: Carlos
authors: C
authors: Cavaleiro
authors: Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, 3000-548 Coimbra, Portugal. Electronic address: laranjin@ci.uc.pt.
authors: João
authors: J
authors: Laranjinha
mesh_terms: D000328:Adult; D000818:Animals; D004032:Diet; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology; D005746:Gastric Emptying; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D018545:Lactuca; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D000431:Ethanol; C032712:ethyl nitrite
keywords: Alcoholic beverages; Dietary nitrate; Ethyl nitrite; Nitric oxide