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| ID | Type | Description | Link |
|---|---|---|---|
| LNMMA-UU-02 | Other Grant/Funding Number | Uppsala Univ, Bengt Ihre Fund, Swedish Soc of Medicine |
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| Name | Class |
|---|---|
| Bengt Ihre Foundation | OTHER |
| The Swedish Society of Medicine | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nitric oxide synthase (NOS) inhibition | Experimental | After a control period of 4 hours, intervention with L-NMMA (10 mg/kg IV) is done and recording continued for 4 hours. |
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| Saline | Sham Comparator | After a control period of 4 hours, intervention with saline is done and recording continued for 4 hours. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-Nitro-Monomethyl-Arginine (LNMMA) 10 mg/kg IV | Biological |
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| Measure | Description | Time Frame |
|---|---|---|
| Effect on phases I-III of the migrating motor complex | NO is considered to be of importance for gastrointestinal motility. The MMC is measured as a biomarker of regulatory functions of gastrointestinal motility. Inhibition of the elaboration of NO by use of LNMMA is used to draw conclusions about the importance of NO for regulation of gastrointestinal motility. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| Reduced exhaled NO after administration of NO synthase inhibitor LNMMA | After administration of a Nitric oxide synthase (NOS) inhibitor exhaled NO is used as a marker of reduced NOS activity. | 1 year |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Per M Hellstrom, MD, prof | Uppsala University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Uppsala University | Uppsala | Uppsala County | 75185 | Sweden |
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| ID | Term |
|---|---|
| D019323 | omega-N-Methylarginine |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D001120 | Arginine |
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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| saline |
| Biological |
|
| D000599 |
| Amino Acids, Diamino |
| D000601 | Amino Acids, Essential |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |