Endogenous nitric oxide modulates small intestinal nutrient transit and activity in healthy adult humans

OBJECTIVE: Nitric oxide (NO) mechanisms have been shown to modulate fasting small intestinal motility in humans, but a role in the regulation of human postprandial small intestinal motility has not been assessed. The aim of this study was to evaluate the effect of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on the regulation of small intestinal nutrient transit and postprandial small intestinal motility in healthy humans. MATERIAL AND METHODS: Seven healthy male volunteers (18-27 years) underwent antroduodenal manometry recordings for 4 h on 2 occasions after intraduodenal instillation of a 500 KJ 120 Kcal] test meal. The meal was administered 15 min after the commencement of a 60-min intravenous infusion of L-NMMA (4 mg kg-1 h-1) or saline (0.9%). Studies were separated, performed in randomized order and >3 days apart. The frequency and amplitude of duodenal pressure waves together with time to return of fasting motility (phase III) was determined. On each day, small intestinal transit was measured using a lactulose breath test. RESULTS: The test meal interrupted fasting small intestinal motility in all subjects. The time to recurrence of fasting motility following its postprandial disruption was similar (L-NMMA versus saline 1.6+/-0.2 h versus 1.9+/-0.1 h; p>0.05). Duodenocaecal transit was delayed by infusion of L-NMMA compared with saline (L-NMMA versus saline 92.1+/-3.9 min versus 66.4+/-6.4 min; p<0.005). Infusion of L-NMMA significantly increased the frequency (L-NMMA versus saline 50.4+/-6.6 versus 34.8+/-5.5 waves per 30 min; p<0.05) and amplitude (L-NMMA versus saline 20.4+/-1.5 versus 15.5+/-1.1 mmHg; p<0.01) of duodenal pressure waves. CONCLUSIONS: These data suggest that endogenous NO may play a role in the regulation of small intestinal nutrient transit by regulating small intestinal motility in healthy individuals.