Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Med. 2010 Mar;16(3):279-85. doi: 10.1038/nm.2092. Epub 2010 Feb 28.

Kynurenine is an endothelium-derived relaxing factor produced during inflammation.

Author information

  • 1Centre for Vascular Research, School of Medical Sciences (Pathology) and Bosch Institute, Faculty of Medicine, University of Sydney, Sydney, Australia.

Erratum in

  • Nat Med. 2010 May;16(5):607.

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-gamma, 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.

Comment in

PMID:
20190767
[PubMed - indexed for MEDLINE]
PMCID:
PMC3556275
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Write to the Help Desk