Nitric oxide synthase is downregulated, while haem oxygenase is increased, in patients with septic shock

Reade, M. C., Millo, J. L., Young, J. D. and Boyd, C. A. R. (2005) Nitric oxide synthase is downregulated, while haem oxygenase is increased, in patients with septic shock. British Journal of Anaesthesia, 94 4: 468-473. doi:10.1093/bja/aei082


Author Reade, M. C.
Millo, J. L.
Young, J. D.
Boyd, C. A. R.
Title Nitric oxide synthase is downregulated, while haem oxygenase is increased, in patients with septic shock
Journal name British Journal of Anaesthesia   Check publisher's open access policy
ISSN 0007-0912
1471-6771
Publication date 2005-04
Sub-type Article (original research)
DOI 10.1093/bja/aei082
Volume 94
Issue 4
Start page 468
End page 473
Total pages 6
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Background: The vasodilatation characteristic of human septic shock is conventionally attributed to increased nitric oxide production, primarily by extrapolation of animal and human in vitro studies. There are no conclusive studies of human disease, and the cellular source of nitric oxide in human sepsis is not known. Haem oxygenase is upregulated by oxidative stress, but little is known about haem oxygenase expression in human sepsis. Haem oxygenase may modulate nitric oxide production, and may also have a direct effect on vascular tone.

Methods: Mesenteric arterial smooth muscle (ASM) (obtained during laparotomy) and peripheral blood mononuclear cells (PBMCs) were obtained from patients with early septic shock and from control patients. mRNA levels were determined by real-time RT-PCR.

Results: mRNA for inducible and endothelial nitric oxide synthase was reduced in both ASM and PBMCs from septic patients. In contrast, inducible haem oxygenase mRNA was increased in sepsis in both cell types.

Conclusions: These results suggest that, rather than being induced, the enzymes which produce nitric oxide are reduced at this time point in human septic shock. Thus many of the in vitro models of sepsis studied to date may not fully replicate human disease. The increase in haem oxygenase expression confirms that these cells have been subjected to oxidative stress in sepsis. The activity of induced haem oxygenase may limit nitric oxide production, while possibly causing vasodilation through production of carbon monoxide.
Keyword Blood, peripheral blood mononuclear cells
Enzymes, haem oxygenase
Measurement techniques, PCR
Muscle, vascular, arterial
Pharmacology, nitric oxide
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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