Journal article
Role of Hydrogen Peroxide and the Impact of Glutathione Peroxidase-1 in Regulation of Cerebral Vascular Tone
Journal of cerebral blood flow and metabolism, Vol.29(6), pp.1130-1137
06/2009
DOI: 10.1038/jcbfm.2009.37
PMCID: PMC2852621
PMID: 19352401
Abstract
Although arachidonic acid (AA) has diverse vascular effects, the mechanisms that mediate these effects are incompletely defined. The goal of the present study was to use genetic approaches to examine the role of hydrogen peroxide (H
2
O
2
), glutathione peroxidase (Gpx1, which degrades H
2
O
2
), and CuZn-superoxide dismutase (SOD1, which produces H
2
O
2
from superoxide) in mediating and determining vascular responses to AA. In basilar arteries in vitro, AA produced dilation in non-transgenic mice and this response was markedly reduced in transgenic mice overexpressing Gpx1 (Gpx1 Tg) or in mice genetically deficient in SOD1. For example, AA (1 nM to 1 µM) dilated the basilar artery and this response was reduced by about 90% in Gpx1 Tg mice (P<0.01), while responses to acetylcholine were not altered. Dilation of cerebral arterioles in vivo in response to AA was inhibited by ~50% by treatment with catalase (300 U/ml)(P<0.05) and reduced by as much as 90% in Gpx1 Tg mice compared to controls (P<0.05). These results provide the first evidence that Gpx1 has functional effects in the cerebral circulation and that AA-induced vascular effects are mediated by H
2
O
2
produced by SOD1. In contrast, cerebral vascular responses to the endothelium-dependent agonist acetylcholine are not mediated by H
2
O
2
.
Details
- Title: Subtitle
- Role of Hydrogen Peroxide and the Impact of Glutathione Peroxidase-1 in Regulation of Cerebral Vascular Tone
- Creators
- Mary L Modrick - Department of Internal Medicine, Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242Sean P Didion - Department of Internal Medicine, Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242Cynthia M Lynch - Department of Internal Medicine, Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242Sanjana Dayal - Department of Internal Medicine, Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242Steven R Lentz - Department of Internal Medicine, Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242Frank M Faraci - Department of Internal Medicine, Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Journal of cerebral blood flow and metabolism, Vol.29(6), pp.1130-1137
- DOI
- 10.1038/jcbfm.2009.37
- PMID
- 19352401
- PMCID
- PMC2852621
- ISSN
- 0271-678X
- eISSN
- 1559-7016
- Language
- English
- Date published
- 06/2009
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Iowa Neuroscience Institute; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040395302771
Metrics
20 Record Views