Role of endogenous nitric oxide in regulating antropyloroduodenal motility in humans

Abstract

OBJECTIVES: Previously we demonstrated the involvement of nitric oxide (NO) in the regulation of interdigestive small intestinal motility in humans. The role of NO in postprandial motility remains to be studied. Therefore, we investigated the effect of the NO synthase inhibitor N G-monomethyl- l-arginine (L-NMMA) on antral, pyloric, and small intestinal postprandial motility in healthy volunteers. METHODS: Ten healthy male volunteers (ages 19–29 yr) underwent stationary antropyloroduodenal manometry recording during administration of a placebo or a high dose of L-NMMA (12 mg/kg within 5 min, followed by a maintenance infusion of 6.7 mg/kg/h i.v.) in a double blind, randomized order. Motility was recorded before and after ingestion of a 300-kcal liquid meal. RESULTS: Two and a half minutes (±0.4 min) after infusion of L-NMMA, rapidly propagated phase III-like activity was observed in the proximal duodenum in every subject. Mean propagation velocity was 26 ± 5 cm/min. The duration of the phase III-like activity increased proximally (9.2 ± 1.6 min) to distally (12 ± 1.5 min), whereas the frequencies of contractions were similar in all manometric channels (10.8 ± 0.3/min). Postprandial duodenal motility was disrupted by phase III-like activity in four of 10 subjects (15–58 min after the meal) during L-NMMA infusion, but not during placebo. Antral or pyloric motility and basal pyloric tone were not significantly altered by L-NMMA, relative to the placebo. CONCLUSIONS: We showed that inhibition of NO biosynthesis triggers the onset of a rapidly propagating phase III and shortens the postprandial period, indicating that NO is involved in the modulation of fasting and postprandial small intestinal motility in humans.