Serum nitrates and vasoactive intestinal peptide in patients with gastroesophageal reflux disease

Background: The normal esophageal motility is a balance between excitatory cholinergic “muscarinic” innervations and noncholinergic nonadrenergic inhibitory innervations. The latter is mediated by nitric oxide (NO) and/or vasoactive intestinal polypeptide (VIP). Methods: The study included 50 patients with gastro-esophageal reflux disease (GERD), and 10 healthy controls of matched age and sex. Patients were divided into five groups according to the degree of lower end esophagitis (Savary-Miller classification). Serum VIP was measured using enzyme immunoassay after peptide purification. Serum nitrate as an index of nitric oxide generation was determined biochemically. Results: Serum nitrate and VIP levels were significantly higher in GERD patients than the control group (p< 0.001). Grade 0 serum nitrates was significantly higher than the control group (p< 0.05) with some overlap between the individual values of the two groups. Serum VIP was significantly higher in grade 0 group compared to control group (p< 0.001) with no overlap in the individual values. There was a significant positive correlation between the grade of lower end esophagitis and each of serum nitrate and VIP (p< 0.001), as well as between serum nitrate and each of serum VIP, cigarette smoking index (CSI) and BMI (p< 0.001). Conclusion: Abnormally high levels of serum VIP and NO may have a role in the pathogenesis of GERD. Exposure of esophageal mucosa to noxious effect of acid refluxed due to the relaxant effect of VIP on lower esophageal sphincter may cause increased NO levels. BMI and CSI are risk factors for GERD progression