Nitric Oxide Control of Migrating Motor Complex: L-NMMA Effects in Relation to Receptor Blockades
Condition: Gastrointestinal Motility Disorder; Disturbance of Salivary Secretion
Study type: Interventional
Phase: Phase 1

Summary: 
      The aim is to elucidate how NO works in conjunction with other neurotransmitters to regulate
      the migrating motility complex (MMC). Twenty-two healthy volunteers should undergo
      water-perfused antroduodenojejunal manometry during a control period of 4 h, followed by
      another 4h after a bolus injection of either saline or the NO synthase inhibitor
      NG-monomethyl-L-arginine (L-NMMA, 10 mg/kg intravenously) with or without atropine (1 mg) or
      ondansetron (8 mg). Effects on the MMC pattern are determined. Exhaled and rectal NO is
      monitored throughout the experiments. Effects of L-NMMA on the MMC pattern are analyzed
      against a background of atropine or ondansetron. Blood samples are drawn for analysis of
      simultaneous peptide hormone release into the bloodstream. Peptide hormone release will be
      correlated to the respective motility pattern elicited by LNMMA.
    

Detailed description: 
      Dysregulation of the cyclic motility pattern controlling propulsion during fasting, the
      migrating motor complex (MMC), can result in small intestinal bacterial overgrowth and
      symptoms of intestinal obstruction. Nitric oxide (NO) acts as an inhibitory neurotransmitter
      by relaxation of smooth muscle cells. Little is known on how NO works in conjunction with
      other neurotransmitters to regulate the MMC.

      Methods: Twenty-two healthy volunteers (22-38 years) should undergo antroduodenojejunal
      manometry recordings for 8h, 4h of which as a control period with basal motility recording
      and 4h after a bolus injection of either saline or the NO synthase inhibitor
      NG-monomethyl-L-arginine (L-NMMA, 10 mg/kg intravenously) with or without atropine (1 mg) or
      ondansetron (8 mg). The effects of L-NMMA on the MMC pattern are to be determined. Exhaled
      and rectal NO was monitored throughout the experiments as a means to secure efficient NO
      synthase inhibition.

      Expected results: L-NMMA is expected to increase the intestinal motor activity, either as a
      direct effect on the small muscle cells, or through the release of some motility-stimulating
      gut peptide hormone (motility, ghrelin, somatostatin).

      Expected conclusions: A NO donor, such as nitrite or nitrate which is converted to NO in an
      acidic milieu in the stomach may act as an inhibitor of motility. Thus, swallowed nitrite and
      nitrate from the saliva may contribute to the regulation of gastric emptying and
      gastrointestinal motility.
    

Intervention name(s): L-Nitro-Monomethyl-Arginine (LNMMA) 10 mg/kg IV; saline
Intervention type(s): Biological; Biological
Other intervention name(s): L-NMMA
Intervention MeSH terms: omega-N-Methylarginine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Nitric oxide; Nitric oxide synthase; Gastrointestinal motility; Gut peptide hormones