Role of nitric oxide in the gastric accommodation reflex and in meal induced satiety in humans

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 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).

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.

Figure 1

Pressure-volume relationships during administration of placebo, N^G-monomethyl-l-arginine (l-NMMA) 4 mg/kg/h, or l-NMMA 8 mg/kg/h. No significant changes were observed. MDP, minimal distending pressure.

Figure 2

(A) Mean increase in intraballoon volume in the first 45 minutes after the meal during administration of placebo, N^G-monomethyl-l-arginine (l-NMMA) 4 mg/kg/h, or l-NMMA 8 mg/kg/h. (B) Accommodation to a liquid meal during administration of placebo, l-NMMA 4 mg/kg/h, or l-NMMA 8 mg/kg/h. l-NMMA dose dependently decreased gastric accommodation. *p<0.05 compared with placebo.

Figure 3

(A) Meal induced satiety scores during administration of placebo or N^G-monomethyl-l-arginine (l-NMMA) 8 mg/kg/h (n=11 at each point unless otherwise indicated). (B) Calorie intake at maximum satiety during administration of placebo or l-NMMA 8 mg/kg/h. l-NMMA significantly enhanced meal induced satiety scores and decreased the amount of calories ingested at maximum satiety. *p<0.05 compared with placebo.