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MOTILITY AND VISCERAL SENSATION |
1 Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium
2 Gastrointestinal Pharmacology, Janssen Research Foundation, Beerse, Belgium
Correspondence to:
Correspondence to:
Dr J Tack, Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium;
Jan.Tack{at}med.kuleuven.ac.be
ABSTRACT
Aims: In humans, impaired gastric accommodation is associated with early satiety and weight loss. In animals, accommodation involves activation of gastric nitrergic neurones. Our aim was to study involvement of nitric oxide in gastric accommodation and in meal induced satiety in humans.
Methods: The effect of NG-monomethyl-L-arginine (L-NMMA) 4 mg/kg/h and 8 mg/kg/h on gastric compliance, on sensitivity to distension, and on gastric accommodation was studied with a barostat in double blind, randomised, placebo controlled studies. The effect of L-NMMA 8 mg/kg/h on meal induced satiety was studied using a drinking test.
Results: L-NMMA had no significant effect on fasting compliance and sensitivity. Ingestion of a meal induced a relaxation of 274 (15) ml which was significantly smaller after L-NMMA 4 mg/kg/h (132 (45) ml; p=0.03) or L-NMMA 8 mg/kg/h (82 (72) ml; p=0.03). L-NMMA 8 mg/kg/h significantly decreased the amount of food ingested at maximum satiety from 1058 (67) to 892 (73) kcal (p<0.01).
Conclusion: In humans, fasting gastric tone and sensitivity to distension are not influenced by nitric oxide synthase inhibition, but the gastric accommodation reflex involves activation of nitrergic neurones. Inhibition of nitric oxide synthase impairs accommodation and enhances meal induced satiety.
Keywords: nitric oxide; gastric accommodation; satiety
Abbreviations: MDP, minimal distending pressure; L-NMMA; NG-monomethyl-L-arginine; NO, nitric oxide; VIP, vasoactive intestinal polypeptide; 5-HT, 5-hydroxytryptamine
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