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Is kynurenine a novel and important vasodilator in human septic shock?

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Patients (n = 16) with septic shock had IDO activity assessed (expressed as the ratio of Kyn to Trp) and the severity of their hypotension determined (expressed by inotrope requirement) during the course of illness... Patients' inotrope requirement correlated with IDO activity (p < 0.001)... IDO activity increased by up to 9-fold with sepsis and was significantly higher than in the two control groups (Figure 1)... In mice, endotoxemia led to hypotension, endothelial IDO expression in resistance vessels, and increased IDO activity... In both IDOand the 1MT-pretreated animals, hypotension was attenuated significantly compared to wild-type controls (Figure 2)... Kyn dose-dependently dilated mouse aortic rings, whereas Trp only dilated arteries from septic mice when IDO was expressed... Trp metabolites of the Kyn pathway other than Kyn were not vasoactive... Separate mechanistic studies indicated that Kyn relaxed blood vessels through activation of sGC and adenylate cyclase... This study shows a significant correlation between IDO activity and hypotension in human septic shock, and that Kyn may act as a previously unrecognized and important vasodilator contributing to hypotension in sepsis.

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IDO activity in sepsis.
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Figure 1: IDO activity in sepsis.

Mentions: Patients' inotrope requirement correlated with IDO activity (p < 0.001). IDO activity increased by up to 9-fold with sepsis and was significantly higher than in the two control groups (Figure 1). In mice, endotoxemia led to hypotension, endothelial IDO expression in resistance vessels, and increased IDO activity. In both IDO-/- and the 1MT-pretreated animals, hypotension was attenuated significantly compared to wild-type controls (Figure 2). Similarly, administration of 1 MT to hypotensive mice restored blood pressure to normal. Kyn dose-dependently dilated mouse aortic rings, whereas Trp only dilated arteries from septic mice when IDO was expressed. Trp metabolites of the Kyn pathway other than Kyn were not vasoactive. Separate mechanistic studies indicated that Kyn relaxed blood vessels through activation of sGC and adenylate cyclase.


Is kynurenine a novel and important vasodilator in human septic shock?
IDO activity in sepsis.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3313386&req=5

Figure 1: IDO activity in sepsis.
Mentions: Patients' inotrope requirement correlated with IDO activity (p < 0.001). IDO activity increased by up to 9-fold with sepsis and was significantly higher than in the two control groups (Figure 1). In mice, endotoxemia led to hypotension, endothelial IDO expression in resistance vessels, and increased IDO activity. In both IDO-/- and the 1MT-pretreated animals, hypotension was attenuated significantly compared to wild-type controls (Figure 2). Similarly, administration of 1 MT to hypotensive mice restored blood pressure to normal. Kyn dose-dependently dilated mouse aortic rings, whereas Trp only dilated arteries from septic mice when IDO was expressed. Trp metabolites of the Kyn pathway other than Kyn were not vasoactive. Separate mechanistic studies indicated that Kyn relaxed blood vessels through activation of sGC and adenylate cyclase.

View Article: PubMed Central - HTML

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Patients (n = 16) with septic shock had IDO activity assessed (expressed as the ratio of Kyn to Trp) and the severity of their hypotension determined (expressed by inotrope requirement) during the course of illness... Patients' inotrope requirement correlated with IDO activity (p < 0.001)... IDO activity increased by up to 9-fold with sepsis and was significantly higher than in the two control groups (Figure 1)... In mice, endotoxemia led to hypotension, endothelial IDO expression in resistance vessels, and increased IDO activity... In both IDOand the 1MT-pretreated animals, hypotension was attenuated significantly compared to wild-type controls (Figure 2)... Kyn dose-dependently dilated mouse aortic rings, whereas Trp only dilated arteries from septic mice when IDO was expressed... Trp metabolites of the Kyn pathway other than Kyn were not vasoactive... Separate mechanistic studies indicated that Kyn relaxed blood vessels through activation of sGC and adenylate cyclase... This study shows a significant correlation between IDO activity and hypotension in human septic shock, and that Kyn may act as a previously unrecognized and important vasodilator contributing to hypotension in sepsis.

No MeSH data available.


Related in: MedlinePlus