Role of nitric oxide in the gastric accommodation reflex and in meal induced satiety in humans.
OBJECTIVE
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 N(G)-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).


CONCLUSIONS
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.
Department of Internal Medicine, Division of Gastroenterology, University Hospital Gasthuisberg, University of Leuven, Leuven, Belgium. Jan.Tack@med.kuleuven.ac.be
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J
Tack
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Demedts
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Meulemans
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Schuurkes
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J
Janssens
D000222:Adaptation, Physiological / Q000187:drug effects*; D000328:Adult; D004311:Double-Blind Method; D004435:Eating / Q000502:physiology; D004791:Enzyme Inhibitors; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012527:Satiation / Q000187:drug effects*; D013270:Stomach / Q000502:physiology; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase