Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans.
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 alpha(2)-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 alpha(2)-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.
Bharucha
Adil E
AE
Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic, 200 First St. S.W., Rochester, MN 55905, USA. bharucha.adil@mayo.edu
Charkoudian
Nisha
N
Andrews
Christopher N
CN
Camilleri
Michael
M
Sletten
David
D
Zinsmeister
Alan R
AR
Low
Phillip A
PA
D000293:Adolescent; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage*; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D054795:Incretins / Q000008:administration & dosage / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000294:innervation; D009569:Nitric Oxide / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects; D015016:Yohimbine / Q000008:administration & dosage*; D019323:omega-N-Methylarginine / Q000008:administration & dosage
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D002395:Catecholamines; D004791:Enzyme Inhibitors; D054795:Incretins; D019323:omega-N-Methylarginine; D015016:Yohimbine; D009569:Nitric Oxide; D052216:Glucagon-Like Peptide 1