Effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on antropyloroduodenal motility and appetite in response to intraduodenal lipid infusion in humans

Background: Studies in animals indicate that endogenous nitric oxide (NO) i s an important inhibitory neurotransmitter in the gastrointestinal tract an d that it modulates food intake. We evaluate the role of NO mechanisms in m ediating the effects of small intestinal nutrients on antropyloroduodenal m otility and appetite in humans. Methods: On 2 separate days, 8 healthy adul t men received intravenous L-NAME 180 mug/kg/h or 0.9% saline (0-150 min); between 30 min and 120 min, an intraduodenal lipid infusion (2 kcal/min) wa s administered, and at 120 min subjects were offered a buffet meal (120-150 min). Antropyloroduodenal pressures were measured with a sleeve/sidehole m anometric assembly. During the infusions, perceptions of hunger and fullnes s were assessed with visual analog questionnaires and amount and macronutri ent content of food consumed at the buffet meal were quantified. Blood pres sure and heart rate were monitored at regular intervals. Results: Intraduod enal lipid infusion was associated with increases in fullness (P < 0.05) an d in frequency of isolated pyloric pressure waves (P < 0.05) and basal pylo ric pressure (P < 0.05); and decreases in hunger (P < 0.05) and in frequenc y of antral (P < 0.05) and duodenal (P < 0.05) pressure waves. I.-NAME incr eased diastolic blood pressure (P = 0.08) and decreased heart rate (P < 0.0 5), but had no effect on antropyloroduodenal pressures or food intake. Conc lusions: Intravenous administration of the systemic NO synthase inhibitor, L-NAME, in a dose that affects cardiovascular function in healthy humans do es not modify the antropyloroduodenal motor and appetite responses to intra duodenal lipid infusion.