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The nitric oxide synthase inhibitor, N g ‐nitro‐ l ‐arginine‐methyl‐ester, attenuates the delay in gastric emptying induced by hyperglycaemia in healthy humans
Author(s) -
Kuo P.,
Gentilcore D.,
Nair N.,
Stevens J. E.,
Wishart J. M.,
Lange K.,
Gilja O. H.,
Hausken T.,
Horowitz M.,
Jones K. L.,
Rayner C. K.
Publication year - 2009
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2009.01321.x
Subject(s) - postprandial , gastric emptying , medicine , placebo , antrum , endocrinology , nitric oxide , pylorus , motility , nitric oxide synthase , insulin , gastroenterology , stomach , biology , alternative medicine , pathology , genetics
The aim of this study was to determine whether the nitric oxide (NO) synthase inhibitor, N g ‐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 ( P < 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); P < 0.01]; l ‐NAME suppressed postprandial antral motility [motility index: 3.6 ± 0.2 ( l ‐NAME) vs 5.1 ± 0.2 (placebo); P < 0.001]. Postprandial basal pyloric pressure was higher during hyperglycaemia ( P < 0.001), and lower after administration of l ‐NAME ( P < 0.001). Slowing of gastric emptying induced by hyperglycaemia is mediated by NO, and may involve the modulation of tonic pyloric activity.