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- Title
Kynurenine is an endothelium-derived relaxing factor produced during inflammation.
- Authors
Yutang Wang; Hanzhong Liu; 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 Jr., John F.; Hunt, Nicholas H.; Stocker, Roland
- Abstract
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.
- Subjects
BLOOD vessels; HOMEOSTASIS; MOUSE diseases; TRYPTOPHAN; KYNURENINE; ENDOTOXEMIA; BLOOD pressure
- Publication
Nature Medicine, 2010, Vol 16, Issue 3, p279
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm.2092