We hypothesized that the inhibitory neurotransmitters nitric oxide (NO
) and vasoactive intestinal peptide (VIP) may play a role in the disru
pted gastrointestinal motility of endotoxemia. Strain gauge transducer
s on the stomach and small intestine of dogs determined interdigestive
gastrointestinal motility. Tissue levels of NO synthase and VIP and s
erum levels of nitrite/nitrate (NO2-INO3-) and VIP were measured. Foll
owing completion of the baseline studies, dogs were given a single dos
e of E. coli lipopolysaccharide, 200 mu g/kg intravenously, and the st
udies were repeated for the next three days. Following endotoxin bolus
, the migrating motor complex (MMC) was delayed for two days while ser
um VIP was increased on postendotoxin day I and serum NO2-/NO3- was in
creased on postendotoxin day 2. There were no changes in gut smooth mu
scle levels of NO synthase or VIP. We conclude that a single, subletha
l dose of endotoxin results in prolongation of the MMC with distinct b
ut independent increases in serum levels of VIP and NO2-/NO3-.