Endotoxin induces nitric oxide (NO.) synthase and alters gastrointestinal f
unctions. 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/wit
hout aminoguanidine (AG). Oesophageal manometry was performed and tissue ba
th studies were performed with muscle strips from the oesophagus and lower
oesophageal sphincter (LOS). Plasma nitrite/nitrate concentrations were det
ermined. The amplitudes of peristaltic pressure waves, resting LOS pressure
and the percentage LOS relaxations were diminished by LPS. AG attenuated t
he decrease in amplitude of oesophageal pressure waves, LOS pressure, and p
ercentage relaxation of LOS brought about by LPS. LPS decreased electrical
field stimulation (EFS)-induced relaxation of LOS muscle. AG attenuated thi
s decrease in LOS relaxation. The off-response of transverse oesophageal mu
scle strips was decreased, and AG antagonized this effect. Plasma concentra
tions of nitrite/nitrate were increased. The increase in plasma nitrite/nit
rate was attenuated by AG. These studies support the hypothesis that endoto
xin modulates oesophageal motor function by increasing NO production and su
ggest that this results from the induction of iNOS.