title: The NO/cGMP pathway in duodenal motor, mechano- and chemosensory responses to acid: A randomized, placebo-controlled study with sildenafil in healthy volunteers.
abstract: BACKGROUND
  Altered duodenal sensorimotor responses to acid have been reported in a subset of patients with functional dyspepsia. To investigate whether NO is involved in these abnormalities, the effect of sildenafil (activates the NO pathway) on duodenal motor and sensory responses to acid in healthy humans was evaluated.
  
  
  METHODS
  A barostat-manometry catheter including an infusion tube was positioned in the duodenum of 12 healthy volunteers. Duodenal motility and dyspeptic symptoms were evaluated during the whole study. A first series of stepwise isobaric distensions was performed while participants scored their perception of upper abdominal sensations at the end of every distension step. Next, the duodenum was infused with sildenafil 50 mg or saline, followed by duodenal acid infusion. During duodenal acidification, a second sequence of stepwise isobaric distensions with the assessment of sensations was repeated.
  
  
  RESULTS
  Acid infusion did not induce dyspeptic symptoms with both placebo and sildenafil pretreatment. Duodenal motility decreased after sildenafil infusion, whereas it was not affected by placebo. Acid-induced increase in motility was, however, observed in both conditions, and no difference between the conditions was found. Duodenal acidification decreased thresholds for discomfort and increased perception scores during duodenal distensions in both groups, but again no difference was observed between placebo and sildenafil pretreatment.
  
  
  CONCLUSIONS
  Sildenafil does not affect duodenal motor, mechanosensory, and chemosensory responses to acid in healthy controls. Therefore, it is less likely that the NO pathway plays a role in the altered response to acid in functional dyspepsia patients.
authors.affiliation: Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: K J
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
authors.forename: H
authors.identifier: http://orcid.org/0000-0002-8832-7002
authors.initials: H
authors.lastname: Vanheel
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Vanuytsel
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Vos
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
authors.forename: J
authors.identifier: http://orcid.org/0000-0002-3206-6704
authors.initials: J
authors.lastname: Tack
mesh_terms: D000328:Adult; D006152:Cyclic GMP / Q000378:metabolism; D004311:Double-Blind Method; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism*; D004415:Dyspepsia / Q000503:physiopathology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D064368:Healthy Volunteers; D006801:Humans; D006851:Hydrochloric Acid / Q000633:toxicity*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D000068677:Sildenafil Citrate / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D006152:Cyclic GMP; D006851:Hydrochloric Acid
keywords: Sildenafil; chemosensitivity; duodenal acid; mechanosensitivity; motility