Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans
- 1 September 2008
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Vol. 295 (3), R874-R880
- https://doi.org/10.1152/ajpregu.00153.2008
Abstract
Glucagon-like peptide-1 (GLP-1), an incretin, which is used to treat diabetes mellitus in humans, inhibited vagal activity and activated nitrergic pathways. In rats, GLP-1 also increased sympathetic activity, heart rate, and blood pressure (BP). However, the effects of GLP-1 on sympathetic activity in humans are unknown. Our aims were to assess the effects of a GLP-1 agonist with or without α2-adrenergic or -nitrergic blockade on autonomic nervous functions in humans. In this double-blind study, 48 healthy volunteers were randomized to GLP-1-(7-36) amide, the nitric oxide synthase (NOS) inhibitor N G-monomethyl-l-arginine acetate (l-NMMA), the α2-adrenergic antagonist yohimbine, or placebo (i.e., saline), alone or in combination. Hemodynamic parameters, plasma catecholamines, and cardiac sympathetic and parasympathetic modulation were measured by spectral analysis of heart rate. Thereafter, the effects of GLP-1-(7-36) amide on muscle sympathetic nerve activity (MSNA) were assessed by microneurography in seven subjects. GLP-1 increased ( P = 0.02) MSNA but did not affect cardiac sympathetic or parasympathetic indices, as assessed by spectral analysis. Yohimbine increased plasma catecholamines and the low-frequency (LF) component of heart rate power spectrum, suggesting increased cardiac sympathetic activity. l-NMMA increased the BP and reduced the heart rate but did not affect the balance between sympathetic and parasympathetic activity. GLP-1 increases skeletal muscle sympathetic nerve activity but does not appear to affect cardiac sympathetic or parasympathetic activity in humans.Keywords
This publication has 57 references indexed in Scilit:
- Beneficial effects of GLP-1 on endothelial function in humans: dampening by glyburide but not by glimepirideAmerican Journal of Physiology-Endocrinology and Metabolism, 2007
- Effects of glucagon‐like peptide‐1 and sympathetic stimulation on gastric accommodation in humans1Neurogastroenterology & Motility, 2007
- A Possible Role of GLP-1 in the Pathophysiology of Early Dumping SyndromeDigestive Diseases and Sciences, 2005
- Spectral Analysis of Blood Pressure and Heart Rate Variability in Evaluating Cardiovascular RegulationHypertension, 1995
- Tissue‐specific expression of the human receptor for glucagon‐like peptide‐I: brain, heart and pancreatic forms have the same deduced amino acid sequencesFEBS Letters, 1995
- Nitric oxide release accounts for insulin's vascular effects in humans.JCI Insight, 1994
- Insulin blunts sympathetic vasoconstriction through the alpha 2-adrenergic pathway in humans.Hypertension, 1994
- Spectral analysis of heart rate variability in the assessment of autonomic diabetic neuropathyJournal of the Autonomic Nervous System, 1988
- Autonomic Neural Dysfunction in Recently Diagnosed Diabetic SubjectsDiabetes Care, 1984
- Influence of yohimbine on blood pressure, autonomic reflexes, and plasma catecholamines in humans.Hypertension, 1983