Nitrogenous chemicals generated from acidification of saliva influence transient lower oesophageal sphincter relaxations

Abstract

Objective. Saliva contains high concentrations of nitrite derived from the enterosalivary recirculation of dietary nitrate and its reduction by buccal bacteria. Acidic gastric juice converts the swallowed nitrite to varying proportions of nitrous acid and nitric oxide (NO) depending upon ascorbic acid availability. Neuronally generated NO is the key in the pathway of transient lower oesophageal sphincter relaxations in vivo. Furthermore, in vitro NO and nitrous acid relax the smooth muscle of the stomach, lower oesophageal sphincter (LOS) and oesophageal body. The objective of this article was to determine whether luminal administration of NO or nitrous acid affects the generation of transient LOS relaxations following a meal. Material and methods. Fifteen healthy subjects were studied on three separate days. A manometry catheter was used to record oesophageal, LOS and gastric pressures, and two oesophageal pH probes were used to record reflux. One of three solutions was infused each day into the cardia after a standardized meal: 1) control solution of hydrochloric acid pH 1.0, 2) nitrous acid and 3) nitrous acid plus ascorbic acid to generate NO. The solutions were randomized and double-blinded. Results. The frequency of transient LOS relaxations was increased by the NO-generating solution at 5.2/h compared with both the control (3.5, p<0.01) and nitrous acid solution (3.1, p<0.0001). The NO-generating solution also increased oesophageal acid exposure to 62.2%, compared with both the control (37.5%, p<0.03) and nitrous acid solution (36.6%, p<0.002). Conclusions. Luminal NO at the gastro-oesophageal junction increases the generation of transient LOS relaxations following a meal. Chemicals generated by the acidification of salivary nitrite may contribute to gastro-oesophageal motility disorders.

• Nitric oxide
• nitrite
• nitrous acid
• transient lower oesophageal sphincter relaxation