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Reference: Reade, Michael Charles., (2002). Arginine transport and other determinants of nitric oxide production in human septic shock. DPhil. University of Oxford.Citable link to this page:

 

Arginine transport and other determinants of nitric oxide production in human septic shock

Abstract: The arterial vasodilation seen in human septic shock is conventionally attributed toincreased nitric oxide (NO) production, primarily by extrapolation of animal andcellular studies. Little is known of the cellular source of NO in human septic shock.Other mediators, such as carbon monoxide (CO), may modulate NO production, andcould also directly contribute to vasodilation.This study has examined the NO and CO synthetic pathways in peripheral bloodmononuclear cells and mesenteric arterial smooth muscle from patients with septicshock, and from non-septic controls.Peripheral blood mononuclear cells from septic patients had increased NO production,though this was perhaps more modest than expected. The transport of arginine, thesubstrate for NO synthase, into these cells was increased; this was due to an increasein the activity of one transporter system, y+. mRNA for a protein encoding y+ activity, CAT2B, was increased in these cells. However, mRNA and protein forinducible and endothelial NO synthase was decreased in sepsis, while inducible hemeoxygenase (the enzyme responsible for CO production) mRNA and protein wasincreased.NO production in arterial smooth muscle from septic patients was reduced, as wasmRNA for inducible and endothelial NO synthase, and the arginine transporter CAT1.There was no increase in inducible NO synthase protein, though there were smallincreases in endothelial NO synthase protein and NO synthase activity. In contrast,both mRNA and protein for inducible heme oxygenase were increased.These results challenge the assumption that NO is central to the pathogenesis ofhuman sepsis. Negative feedback systems for NO production have been demonstratedin cell models. These may be relatively more important in human sepsis. In additionto forming one of these feedback systems, it may be that CO, more than NO, isresponsible for the hypotension observed in these patients.

Type of Award:DPhil Level of Award:Doctoral Awarding Institution: University of Oxford Notes:This thesis was digitised thanks to the generosity of Dr Leonard Polonsky.

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Young, Duncan.More by this contributor

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Duncan YoungMore by this contributor

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 Bibliographic Details

Issue Date: 2002Identifiers

Urn: uuid:abf881fc-3c9a-40b4-89e1-07b8df2067d1

Source identifier: 603824078 Item Description

Type: Thesis;

Language: eng Subjects: Blood cells Research Septicemia Tiny URL: td:603824078

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Author: Reade, Michael Charles. - institutionUniversity of Oxford facultyMedical Sciences Division - - - - Contributors Young, Duncan. Mo

Source: https://ora.ox.ac.uk/objects/uuid:abf881fc-3c9a-40b4-89e1-07b8df2067d1



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