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) is an important inhibitory neurotransmitter in the gastrointestinal tract and that it modulates food intake. We evaluate the role of NO mechanisms in mediating the effects of small intestinal nutrients on antropyloroduodenal motility and appetite in humans.

Methods: On 2 separate days, 8 healthy adult men received intravenous L-NAME 180 microg/kg/h or 0.9% saline (0-150 min); between 30 min and 120 min, an intraduodenal lipid infusion (2 kcal/min) was administered, and at 120 min subjects were offered a buffet meal (120-150 min). Antropyloroduodenal pressures were measured with a sleeve/sidehole manometric assembly. During the infusions, perceptions of hunger and fullness were assessed with visual analog questionnaires and amount and macronutrient content of food consumed at the buffet meal were quantified. Blood pressure and heart rate were monitored at regular intervals.

Results: Intraduodenal lipid infusion was associated with increases in fullness (P < 0.05) and in frequency of isolated pyloric pressure waves (P < 0.05) and basal pyloric pressure (P < 0.05); and decreases in hunger (P < 0.05) and in frequency of antral (P < 0.05) and duodenal (P < 0.05) pressure waves. L-NAME increased diastolic blood pressure (P = 0.08) and decreased heart rate (P < 0.05), but had no effect on antropyloroduodenal pressures or food intake.

Conclusions: Intravenous administration of the systemic NO synthase inhibitor, L-NAME, in a dose that affects cardiovascular function in healthy humans does not modify the antropyloroduodenal motor and appetite responses to intraduodenal lipid infusion.