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Am J Physiol Gastrointest Liver Physiol 288: G1227-G1232, 2005. First published February 3, 2005; doi:10.1152/ajpgi.00511.2004
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NEUROREGULATION AND MOTILITY

Role of nitric oxide mechanisms in gastric emptying of, and the blood pressure and glycemic responses to, oral glucose in healthy older subjects

Diana Gentilcore,1 Renuka Visvanathan,1,2 Antonietta Russo,1 Reawika Chaikomin,1 Julie E. Stevens,1 Judith M. Wishart,1 Anne Tonkin,3 Michael Horowitz,1 and Karen L. Jones1

1Department of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide; 2Aged and Extended Care Services, The Queen Elizabeth Hospital, Woodville, and 3Department of Clinical Pharmacology, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, Australia

Submitted 11 November 2004 ; accepted in final form 29 January 2005

The primary aims of this study were to evaluate the effects of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on gastric emptying (GE) of, and the blood pressure (BP), glycemic, insulin, and incretin responses to, oral glucose in older subjects. Eight healthy subjects (4 males and 4 females, aged 70.9 ± 1.3 yr) were studied on two separate days, in double-blind, randomized order. Subjects received an intravenous infusion of either L-NAME (180 µg·kg–1·h–1) or saline (0.9%) at a rate of 3 ml/min for 150 min. Thirty minutes after the commencement of the infusion (0 min), subjects consumed a 300-ml drink containing 50 g glucose labeled with 20 MBq 99mTc-sulfur colloid, while sitting in front of a gamma camera. GE, BP (systolic and diastolic), heart rate (HR), blood glucose, plasma insulin, and incretin hormones, glucose-dependant insulinotropic-polypeptide (GIP), and glucagon-like peptide-1 (GLP-1), were measured. L-NAME had no effect on GE, GIP, and GLP-1. Between –30 and 0 min L-NAME had no effect on BP or HR. After the drink (0–60 min), systolic and diastolic BP fell (P < 0.05) and HR increased (P < 0.01) during saline; these effects were attenuated (P < 0.001) by L-NAME. Blood glucose levels between 90 and 150 min were higher (P < 0.001) and plasma insulin were between 15 and 150 min less (P < 0.001) after L-NAME. The fall in BP, increase in HR, and stimulation of insulin secretion by oral glucose in older subjects were mediated by NO mechanisms by an effect unrelated to GE or changes in incretin hormones.

NG-nitro-L-arginine methyl ester; postprandial; hypotension; elderly



Address for reprint requests and other correspondence: K. L. Jones, Dept. of Medicine, Univ. of Adelaide, Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000, Australia (E-mail: karen.jones{at}adelaide.edu.au)




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