Abstract
Genetic Evidence that Cerebrovascular Responses to Arachidonic Acid are Mediated by Hydrogen Peroxide Produced by SOD‐1
The FASEB journal, Vol.21(6), pp.A1384-A1385
2007
DOI: 10.1096/fasebj.21.6.A1384-d
Abstract
Arachidonic acid (AA) is a key molecule in vascular biology. Divergent mechanisms, including generation of reactive oxygen species and hydrogen peroxide (H2O2), have been proposed to mediate effects of AA on vascular tone. In this study, mice overexpressing glutathione peroxidase (GPx‐1), which degrades H2O2, were used to examine mechanisms by which AA affects blood vessels. Real‐time RT‐PCR indicated that vascular expression of GPx‐1 mRNA was increased 2.5‐fold in transgenic (Tg) mice compared to non‐transgenic (non‐Tg) littermates. In basilar arteries in vitro and in cerebral arterioles in vivo, AA produced dilation in non‐Tg mice and this response was markedly reduced in Tg mice (P<0.05). For example, 1 μM AA dilated the basilar artery by 53±5 and 7±2% in non‐Tg and GPx‐1 Tg mice, respectively. Responses to AA were also greatly reduced in mice deficient in superoxide dismutase (SOD‐1, which converts superoxide to H2O2) suggesting that SOD‐1 is the primary source of H2O2. In contrast, vasodilation to acetylcholine was not altered in GPx‐1 Tg mice suggesting that H2O2 plays no role in this response. Thus, overexpression of GPx‐1 almost completely prevents AA‐induced effects on cerebral vascular tone. These results provide the first evidence that GPx‐1 has functional effects in the cerebral circulation and that H2O2, produced by SOD‐1, is a key mediator of AA‐induced dilation in cerebral arteries and microvessels.
Details
- Title: Subtitle
- Genetic Evidence that Cerebrovascular Responses to Arachidonic Acid are Mediated by Hydrogen Peroxide Produced by SOD‐1
- Creators
- Frank M Faraci - University of IowaMary L Modrick - University of IowaCynthia Lynch - University of IowaSanjana Dayal - University of IowaSteven R Lentz - University of IowaSean P Didion - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.21(6), pp.A1384-A1385
- Publisher
- The Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.21.6.A1384-d
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 2007
- Academic Unit
- Neuroscience and Pharmacology; Cardiovascular Medicine; Internal Medicine; Iowa Neuroscience Institute; Hematology, Oncology, and Blood & Marrow Transplantation
- Record Identifier
- 9984071632402771
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