Kynurenine is an endothelium-derived relaxing factor produced during inflammation

Kynurenine, a metabolite produced by the action of the enzyme indoleamine 2,3-dioxygenase on tryptophan, accumulates under inflammatory conditions and has immunomodulatory effects. This study by Yutang Wang et al . describes a new function for kynurenine as an endogenous vasodilator under conditions...

Full description

Saved in:

Bibliographic Details
Published in:	Nature medicine Vol. 16; no. 3; pp. 279 - 285
Main Authors:	Wang, Yutang, Liu, Hanzhong, McKenzie, Gavin, Witting, Paul K, Stasch, Johannes-Peter, Hahn, Michael, Changsirivathanathamrong, Dechaboon, Wu, Ben J, Ball, Helen J, Thomas, Shane R, Kapoor, Vimal, Celermajer, David S, Mellor, Andrew L, Keaney, John F, Hunt, Nicholas H, Stocker, Roland
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01.03.2010 Nature Publishing Group
Subjects:	631/443/1338/1872 631/443/1338/243 631/443/319 692/420/256 Adenylyl Cyclases - metabolism Amino acids Animals Biomedical and Life Sciences Biomedicine Blood pressure Blood Pressure - drug effects Blood Pressure - physiology Cancer Research Coronary Vessels - drug effects Coronary Vessels - physiopathology Dose-Response Relationship, Drug Endothelium Endothelium, Vascular - enzymology Endothelium, Vascular - physiology Endothelium, Vascular - physiopathology Endothelium-Dependent Relaxing Factors - physiology Endothelium-derived relaxing factors Endotoxemia - physiopathology Enzyme Activation - physiology Guanylate Cyclase - metabolism Guanylate Cyclase - physiology Health aspects Indoleamine-Pyrrole 2,3,-Dioxygenase - antagonists & inhibitors Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism Indoleamine-Pyrrole 2,3,-Dioxygenase - physiology Infectious Diseases Inflammation Inflammation - physiopathology Inflammatory diseases Interferon-gamma - physiology Kynurenine - biosynthesis Kynurenine - pharmacology Kynurenine - physiology Malaria - physiopathology Metabolic Diseases Metabolism Mice Mice, Inbred C57BL Molecular Medicine Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - physiology Neurosciences Neurotransmitters Parasites Plasmodium berghei Rats Rats, Inbred SHR Rodents Tryptophan - blood Tryptophan - pharmacology Tryptophan - physiology
ISSN:	1078-8956, 1546-170X, 1546-170X
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Kynurenine, a metabolite produced by the action of the enzyme indoleamine 2,3-dioxygenase on tryptophan, accumulates under inflammatory conditions and has immunomodulatory effects. This study by Yutang Wang et al . describes a new function for kynurenine as an endogenous vasodilator under conditions of systemic inflammation, such as malaria infection and endotoxemia in mice, and provides insight into the molecular mechanisms involved ( pages 265–267 ). Control of blood vessel tone is central to vascular homeostasis. Here we show that metabolism of tryptophan to kynurenine by indoleamine 2,3-dioxygenase (Ido) expressed in endothelial cells contributes to arterial vessel relaxation and the control of blood pressure. Infection of mice with malarial parasites ( Plasmodium berghei ) or induction of endotoxemia in mice led to endothelial expression of Ido, decreased plasma tryptophan concentration, increased kynurenine concentration and hypotension. Pharmacological inhibition of Ido increased blood pressure in systemically inflamed mice but not in mice deficient in Ido or interferon-γ, which is required for Ido induction. Both tryptophan and kynurenine dilated preconstricted porcine coronary arteries; the dilating effect of tryptophan required the presence of active Ido and an intact endothelium, whereas the effect of kynurenine was endothelium independent. The arterial relaxation induced by kynurenine was mediated by activation of the adenylate and soluble guanylate cyclase pathways. Kynurenine administration decreased blood pressure in a dose-dependent manner in spontaneously hypertensive rats. Our results identify tryptophan metabolism by Ido as a new pathway contributing to the regulation of vascular tone.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1078-8956 1546-170X 1546-170X
DOI:	10.1038/nm.2092