Journal article
Glutathione peroxidase-1 plays a major role in protecting against angiotensin II-induced vascular dysfunction
Hypertension (Dallas, Tex. 1979), Vol.51(4), pp.872-877
04/2008
DOI: 10.1161/HYPERTENSIONAHA.107.103572
PMCID: PMC3139513
PMID: 18299484
Abstract
Levels of reactive oxygen species, including hydrogen peroxide(,) increase in blood vessels during hypertension and in response to angiotensin II (Ang II). Although glutathione peroxidases are known to metabolize hydrogen peroxide, the role of glutathione peroxidase during hypertension is poorly defined. We tested the hypothesis that glutathione peroxidase-1 protects against Ang II-induced endothelial dysfunction. Responses of carotid arteries from Gpx1-deficient (Gpx1(+/-) and Gpx1(-/-)) and Gpx1 transgenic mice, and their respective littermate controls, were examined in vitro after overnight incubation with either vehicle or Ang II. Under control conditions, relaxation to acetylcholine (ACh; an endothelium-dependent agonist) was similar in control, Gpx1(+/-), and Gpx1 transgenic mice, whereas in Gpx1(-/-) mice, responses to ACh were impaired. In control mice, ACh-induced vasorelaxation was not affected by 1 nmol/L of Ang II. In contrast, relaxation to ACh in arteries from Gpx1(+/-) mice was inhibited by approximately 60% after treatment with 1 nmol/L of Ang II, indicating that Gpx1 haploinsufficiency markedly enhances Ang II-induced endothelial dysfunction. A higher concentration of Ang II (10 nmol/L) selectively impaired relaxation to ACh in arteries from control mice, and this effect was prevented in arteries from Gpx1 transgenic mice or in arteries from control mice treated with polyethylene glycol-catalase (which degrades hydrogen peroxide). Thus, genetic and pharmacological evidence suggests a major role for glutathione peroxidase-1 and hydrogen peroxide in Ang II-induced effects on vascular function.
Details
- Title: Subtitle
- Glutathione peroxidase-1 plays a major role in protecting against angiotensin II-induced vascular dysfunction
- Creators
- Sophocles Chrissobolis - Department of Internal Medicine, Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242-1081, USASean P DidionDale A KinzenbawLaura I SchraderSanjana DayalSteven R LentzFrank M Faraci
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.51(4), pp.872-877
- Publisher
- United States
- DOI
- 10.1161/HYPERTENSIONAHA.107.103572
- PMID
- 18299484
- PMCID
- PMC3139513
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Grant note
- HL-63943 / NHLBI NIH HHS R01 HL038901 / NHLBI NIH HHS P01 NS024621 / NINDS NIH HHS R01 HL038901-21 / NHLBI NIH HHS HL-38901 / NHLBI NIH HHS NS-24621 / NINDS NIH HHS R01 HL063943 / NHLBI NIH HHS P01 HL062984 / NHLBI NIH HHS P01 NS024621-21A1 / NINDS NIH HHS HL-62984 / NHLBI NIH HHS
- Language
- English
- Date published
- 04/2008
- 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
- 9984040018802771
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