The NO/cGMP pathway in duodenal motor, mechano- and chemosensory responses to acid: A randomized, placebo-controlled study with sildenafil in healthy volunteers

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. Key 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 and Inferences 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.