Role of nitric oxide mechanisms in gastric emptying of, and the blood pressure and glycemic responses to, oral glucose in healthy older subjects.
The primary aims of this study were to evaluate the effects of the nitric oxide (NO) synthase inhibitor N(G)-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 mug.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 (99m)Tc-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.
Gentilcore
Diana
D
Dept. of Medicine, Univ. of Adelaide, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia.
Visvanathan
Renuka
R
Russo
Antonietta
A
Chaikomin
Reawika
R
Stevens
Julie E
JE
Wishart
Judith M
JM
Tonkin
Anne
A
Horowitz
Michael
M
Jones
Karen L
KL
D000284:Administration, Oral; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D005947:Glucose / Q000494:pharmacology*; D006339:Heart Rate; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D019518:Postprandial Period
D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester