W2041 Effects of the Nitric Oxide (NO) Synthase Inhibitor, NG-Nitro-L-Arginine-Methyl-Ester (L-NAME), On Delayed Gastric Emptying Induced By Hyperglycaemia in Healthy Humans

Abstract

Acute hyperglycaemia slows gastric emptying, reduces proximal gastric tone, inhibits antral motility, and stimulates pyloric contractions. The mechanisms mediating these effects are unknown, but nitric oxide (NO), a key inhibitory neurotransmitter in the gut, could potentially be involved. Aim: To determine whether the NO synthase inhibitor, L-NAME, reverses the effects of hyperglycaemia on gastric emptying and proximal and distal gastric motility. Methods: Seven healthy volunteers (4 male; age 30.3±3.8 yr; BMI 23.6±1.2 kg/m2) were studied in a 4-way randomised crossover design (hyperglycaemia vs. euglycaemia; L-NAME vs. placebo) after an overnight fast. After positioning a transnasal manometry catheter across the pylorus, the blood glucose was maintained at either 15 mmol/L or 5 mmol/L using a glucose/insulin clamp. Once the blood glucose was stabilised for 30 min, an intravenous infusion of L-NAME (180 mcg/kg/h) or placebo (0.9% saline) was commenced (t = 0) and continued for 150 min. At t = 30, subjects ingested a test drink containing 50g glucose made up to 300ml with water. Gastric emptying and intragastric distribution (proximal and distal stomach retention) were measured using 3-D ultrasound. Antropyloroduodenalmotility was recorded concurrently. Statistical analysis was performed using repeated measures ANOVA. Data presented as mean ± SEM. Results: Gastric half-emptying time (T50) was prolonged on the hyperglycaemia/placebo day compared to the remaining 3 study days, which were no different from each other (127±19min [hyperglycaemia/placebo] vs. 86±7min [hyperglycaemia/L-NAME] vs. 77±12min [euglycaemia/placebo] vs. 81±5min [euglycaemia/ L-NAME]; P = 0.01). The effect of hyperglycaemia on gastric emptying was completely abolished by L-NAME. The rate of total gastric emptying closely correlated to that of proximal (r = 0.970; P < 0.0001), but not distal (P = N.S.), gastric emptying. Fasting antral motility index was suppressed during hyperglycaemia (P < 0.05). Basal pyloric pressure was increased during hyperglycaemia (P < 0.001), and decreased with L-NAME (P < 0.001). Conclusions: Hyperglycaemia-induced delay in gastric emptying is associated with increased proximal retention and increased basal pyloric pressure; these effects are attenuated markedly by L-NAME.