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Cited by 446

The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.

Kynurenine is an endothelium-derived relaxing factor produced during inflammation

Open access
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·2010·Nature Medicine
DOI 10.1038/nm.2092
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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.

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Metadata

Authors
Wang, Y., Liu, H., McKenzie, G., Witting, P. K., Stasch, J.-P., Hahn, M., Changsirivathanathamrong, D., Wu, B. J., Ball, H. J., Thomas, S. R., Kapoor, V., Celermajer, D. S., Mellor, A. L., Keaney, J. F., Hunt, N. H., & Stocker, R.
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2010-02-28
Volume
16
Issue
3
Pages
279-285
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.2092
OpenAlex
W1965240438
Cited by
446
References
54
FWCI
8.19
Type
journal article
Language
en
Open access
green

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