Real-time dynamics of nitric oxide shifts within the esophageal wall

Abstract

Currently, indirect evidence suggests that the neurotransmitter nitric oxide (NO) plays a crucial role in the genesis of aboral propagation of esophageal peristalses during swallowing. However, direct evidence in this regard currently is lacking. This study aimed to assess the feasibility of using NO-selective microprobes to detect real-time NO changes within the esophageal wall of North American opossums (Didelphis virginiana) during normal progressive esophageal peristalsis and induced esophageal dysmotility. Six adult opossums of both sexes (mean weight, 2.28 +/- 0.41 kg) were included in the study. All had normal esophageal motility, as documented by water-perfused esophageal manometry. A calibrated carbon fiber NO-selective microelectrode (ISNOP30, ISNOP100) was placed within the smooth muscle portion of the esophageal wall, and changes in NO levels were measured as redox current in pico-amperes (pA) with the Apollo-4000 NO meter. The dynamics of NO in response to reflexive deglutition were assessed during both normal propagative peristalsis and abnormal esophageal contractions induced by intravenous (i.v.) administration of the neural NO synthase inhibitor L-nitro L-arginine methyl ester (L-NAME) and banding of the gastroesophageal junction (GEJ) for 4-weeks. During normal propagative esophageal peristalsis, a mean change of 2,158.85 +/- 715.93 pA was measured by the NO meter. Intravenous administration of L-NAME and chronic banding of the GEJ induced achalasia-like esophageal contractions. A significantly smaller change in levels of NO was detected within the esophageal wall during dysfunctional motility (331.94 +/- 188.17 pA; p < 0.001) than during normal propagative peristalsis (579 +/- 385 pA; p < 0.001). The results of this study indicate that carbon fiber NO-selective microprobes can successfully measure changes in the concentration of NO, an important inhibitory neurotransmitter, within the esophageal wall and that these preliminary data support the involvement of this crucial neurotransmitter in programming normal propagation of peristaltic waves within the esophagus.