Effect of endotoxin on opossum oesophageal motor function.

Abstract

Endotoxin induces nitric oxide (NO*) synthase and alters gastrointestinal functions. We explored the effect of lipopolysaccharide (LPS) on oesophageal motor function at 6, 12, 24, and 48 h. The effects of inhibiting inducible NO* synthase (iNOS) were studied 12 h after administration of LPS with/without aminoguanidine (AG). Oesophageal manometry was performed and tissue bath studies were performed with muscle strips from the oesophagus and lower oesophageal sphincter (LOS). Plasma nitrite/nitrate concentrations were determined. The amplitudes of peristaltic pressure waves, resting LOS pressure and the percentage LOS relaxations were diminished by LPS. AG attenuated the decrease in amplitude of oesophageal pressure waves, LOS pressure, and percentage relaxation of LOS brought about by LPS. LPS decreased electrical field stimulation (EFS)-induced relaxation of LOS muscle. AG attenuated this decrease in LOS relaxation. The off-response of transverse oesophageal muscle strips was decreased, and AG antagonized this effect. Plasma concentrations of nitrite/nitrate were increased. The increase in plasma nitrite/nitrate was attenuated by AG. These studies support the hypothesis that endotoxin modulates oesophageal motor function by increasing NO production and suggest that this results from the induction of iNOS.