liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Hyperoxia inhibits production of endothelial nitric oxide in humans
Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Hypceoxia causes vasoconstriction in most tissues, but the mechanisms have yet to be elucidated. One hypothesis is that hyperoxia affects the production of free oxygen radicals (ROS), which reduce the concentration of the vasorelaxing agent nitric oxide (NO). It is not clear whether ROS reduce the synthesis of NO or inactivate NO that is already present. We investigated the effects of breathing 100% oxygen on NO-mediated vasodilation. Iontophoresis was used to deliver acetylcholine (ACh) (which stimulates endothelium-dependent production of NO) and sodium nitroprusside (SNP) (a NO-donor) through the skin of healthy volunteers (n=9). The blood flow in the skin was measured with a laser Doppler perfusion imager and dose-response curves were plotted. The drug dose at which 50% of the total perfusion increase was reached was calculated (ED50). The ED50 was significantly higher (right-shifted curve) while breathing oxygen compared with breathing air, when ACh was given by iontophoresis (95% CI 0.26 to 2.2). When ACh iontophoresis was preceded by oral intake of vitamin C (2.5 g daily for 3 days), this effect was abolished. Hyperoxla had no effect on vasodilation after iontophoresis with SNP. These results favour the hypothesis that hyperoxic vasoconstriction is mediated through inhibition of synthesis of NO by free oxygen radicals inside the endothelial cells.

National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-83825OAI: oai:DiVA.org:liu-83825DiVA: diva2:558221
Available from: 2012-10-02 Created: 2012-10-02 Last updated: 2012-10-03Bibliographically approved
In thesis
1. Vascular effects of hyperoxaemia and its mechanisms in man
Open this publication in new window or tab >>Vascular effects of hyperoxaemia and its mechanisms in man
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Most cells in the human body cannot survive without oxygen. The regulation of oxygen delivery to meet demands of tissues remains contentious. The study of supranormallevels of oxygen (hyperoxia/hyperoxaemia) may contribute to the understanding, as mechanisms that are active during normoxia and hypoxia (oxygen deficit) can be assumed to be at least similar, and compensatory mechanisms are kept to a minimum. Hyperoxaemic conditions are often seen clinically, but their effects in the human body are not fully known.

Hyperoxaemia causes vasoconstriction and reduction in heart rate and cardiac output. These effects are thought to be mediated through the endothelium as a result of either increased release, or activity, of vasoconstrictors such as serotonin (5-hydroxytryptamine, 5-HT)), or reduced activity of vasodilators such as prostaglandin E2 and nitric oxide (NO)). 5-HT and NO have been thought to have a central role.

To investigate both its effects and the underlying mechanisms we set up a human non-invasive normobaric hyperoxaemic model. We studied the effects of hyperoxaemia by measuring: peripheral blood flow by venous occlusion plethysmography; skin blood flow by laser Doppler perfusion imaging (LDI); cardiovascular assessments by echocardiography; and oxygen consumption (VO2) by an open circuit exchange system, CPX.

Plasma concentrations of 5-HT and ß-thromboglobulin (ß-TG) were measured to investigate the role of 5-HT during hyperoxaemia. To test the NO-hypothesis we achieved endothelium-dependent and endothelium-independent vasodilatation, using acetylcholine (ACh), and sodium nitroprusside (SNP) iontophoresis, respectively.

Mean calf blood flow decreased linearly to as much as -20% during oxygen breathing. Heart rate and cardiac output decreased, systemic vascular resistance increased, and blood pressure remained unchanged. Hyperoxaemia lessened vasodilatation in the skin induced by current (iontophoresis) and an anaesthetic agent (EMLA®-cream). There was no significant increase in concentrations of either 5-HT or ß-TG during hyperoxia, compared with air. Endothelium-dependent vasodilatation (ACh) was significantly reduced by breathing 100% oxygen. Vitamin C taken orally abolished the effects of oxygen. Hyperoxia did not affect endothelium-independent vasodilatation (SNP).

Hyperoxia affected most parts of the cardiovascular system in man, including perfusion in the skin. Probably the first and most pronounced effect was peripheral vasoconstriction, which could be seen within minutes. Heart rate and cardiac output decreased, possibly secondary to the vasoconstriction, so as to keep the blood pressure constant. There was no evidence that 5-HT had an important role in hyperoxia-mediated responses. On the contrary, the most likely hypothesis is that hyperoxic vasoconstriction is mediated by inhibition of synthesis of NO by free oxygen radicals inside the endothelial cells.

Place, publisher, year, edition, pages
Linköping: Larsson Offsettryck, 2005. 49 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 891
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-31534 (URN)17333 (Local ID)91-85299-00-6 (ISBN)17333 (Archive number)17333 (OAI)
Public defence
2005-04-22, Berzeliussalen, Hälsouniversitetets bibliotek, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-10-03Bibliographically approved

Open Access in DiVA

No full text

Authority records BETA

Rousseau, AndréasHenricson, JoakimSjöberg, Folke

Search in DiVA

By author/editor
Rousseau, AndréasHenricson, JoakimSjöberg, Folke
By organisation
Department of Medicine and CareFaculty of Health SciencesDepartment of Biomedicine and Surgery
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 30 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf