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Kynurenine is an endothelium-derived relaxing factor produced during inflammation
Open accessAbstract
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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Thomas, S. R., Chen, K., & Keaney, J. F. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109107200 · Cited by 381
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Gramaglia, I., Sobolewski, P., Meays, D., Contreras, R., Nolan, J. P., Frangos, J. A., Intaglietta, M., & van der Heyde, H. C. (2006) · Nature Medicine · doi:10.1038/nm1499 · Cited by 215
Cited by
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Kynurenines in the mammalian brain: when physiology meets pathology
Schwarcz, R., Bruno, J. P., Muchowski, P. J., & Wu, H.-Q. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3257 · Cited by 1,530
Salt-responsive gut commensal modulates TH17 axis and disease
Wilck, N., Matus, M. G., Kearney, S. M., Olesen, S. W., Forslund, K., Bartolomaeus, H., Haase, S., Mähler, A., Balogh, A., Markó, L., et al. (2017) · Nature · doi:10.1038/nature24628 · Cited by 1,310
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Munn, D. H., & Mellor, A. L. (2013) · Trends in Immunology · doi:10.1016/j.it.2012.10.001 · Cited by 1,037
Self-citationKynurenines in the CNS: recent advances and new questions
Vécsei, L., Szalárdy, L., Fülöp, F., & Toldi, J. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3793 · Cited by 641
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
- Published
- 2010-02-28
- Volume
- 16
- Issue
- 3
- Pages
- 279-285
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W1965240438
- Cited by
- 446
- References
- 2
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- green
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- 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. (2010). Kynurenine is an endothelium-derived relaxing factor produced during inflammation. Nature Medicine. https://doi.org/10.1038/nm.2092
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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