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We hypothesized that the inhibitory neurotransmitters nitric oxide (NO) and vasoactive intestinal peptide (VIP) may play a role in the disrupted gastrointestinal motility of endotoxemia. Strain gauge transducers on the stomach and small intestine of dogs determined interdigestive gastrointestinal motility. Tissue levels of NO synthase and VIP and serum levels of nitrite/nitrate (NO(2)-/NO(3)-) and VIP were measured. Following completion of the baseline studies, dogs were given a single dose of E. coli lipopolysaccharide, 200 microg/kg intravenously, and the studies were repeated for the next three days. Following endotoxin bolus, the migrating motor complex (MMC) was delayed for two days while serum VIP was increased on postendotoxin day 1 and serum NO(2)-/NO(3)- was increased on postendotoxin day 2. There were no changes in gut smooth muscle levels of NO synthase or VIP. We conclude that a single, sublethal dose of endotoxin results in prolongation of the MMC with distinct but independent increases in serum levels of VIP and NO(2)-/NO(3)-.