The nitric oxide synthase inhibitor, Ng-nitro-l-arginine-methyl-ester, attenuates the delay in gastric emptying induced by hyperglycaemia in healthy humans

Authors


Paul Kuo, Discipline of Medicine, University of Adelaide, Level 6, Eleanor Harrald Building, Royal Adelaide Hospital, Adelaide, Australia.
Tel: +61 08 82225073; fax: +61 08 82233870; e-mail: paul.kuo@adelaide.edu.au

Abstract

Abstract  The aim of this study was to determine whether the nitric oxide (NO) synthase inhibitor, Ng-nitro-l-arginine-methyl-ester (l-NAME), reverses the effects of acute hyperglycaemia on gastric emptying and antropyloroduodenal (APD) motility. The study had a four-way randomized crossover (hyperglycaemia vs euglycaemia; l-NAME vs placebo) design in a clinical laboratory setting. Seven healthy volunteers [four males; age 30.3 ± 3.8 years; body mass index (BMI) 23.6 ± 1.2 kg m−2] were the study subjects. After positioning a transnasal manometry catheter across the pylorus, the blood glucose concentration was maintained at either 15 or 5 mmol L−1 using a glucose/insulin clamp. An intravenous infusion of l-NAME (180 μg kg−1 h−1) or placebo (0.9% saline) was commenced (T = −30 min) and continued for 150 min. At T = −2 min, subjects ingested a drink containing 50 g of glucose made up to 300 mL with water. Gastric emptying was measured using 3D ultrasound, and APD motility using manometry. Hyperglycaemia slowed gastric emptying (< 0.05), and this effect was abolished by l-NAME. l-NAME had no effect on gastric emptying during euglycaemia. Hyperglycaemia suppressed fasting antral motility [motility index: 3.9 ± 0.8 (hyperglycaemia) vs 6.5 ± 0.6 (euglycaemia); < 0.01]; l-NAME suppressed postprandial antral motility [motility index: 3.6 ± 0.2 (l-NAME) vs 5.1 ± 0.2 (placebo); < 0.001]. Postprandial basal pyloric pressure was higher during hyperglycaemia (< 0.001), and lower after administration of l-NAME (< 0.001). Slowing of gastric emptying induced by hyperglycaemia is mediated by NO, and may involve the modulation of tonic pyloric activity.

Ancillary