The nitric oxide synthase inhibitor, Ng-nitro-L-arginine-methyl-ester, attenuates the delay in gastric emptying induced by hyperglycaemia in healthy humans.
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 microg 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.
Kuo
P
P
Discipline of Medicine, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia. paul.kuo@adelaide.edu.au
Gentilcore
D
D
Nair
N
N
Stevens
J E
JE
Wishart
J M
JM
Lange
K
K
Gilja
O H
OH
Hausken
T
T
Horowitz
M
M
Jones
K L
KL
Rayner
C K
CK
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005215:Fasting; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology; D005753:Gastric Mucosa / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D006339:Heart Rate; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D054795:Incretins / Q000097:blood; D007328:Insulin / Q000097:blood; D008297:Male; D008365:Manometry; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010919:Placebos / Q000378:metabolism; D013270:Stomach / Q000000981:diagnostic imaging; D014463:Ultrasonography; D055815:Young Adult
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D054795:Incretins; D007328:Insulin; D010919:Placebos; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester