Journal article
Role of Nox isoforms in angiotensin II-induced oxidative stress and endothelial dysfunction in brain
Journal of applied physiology (1985), Vol.113(2), pp.184-191
07/15/2012
DOI: 10.1152/japplphysiol.00455.2012
PMCID: PMC3774474
PMID: 22628375
Abstract
Angiotensin II (Ang II) promotes vascular disease through several mechanisms including by producing oxidative stress and endothelial dysfunction. Although multiple potential sources of reactive oxygen species exist, the relative importance of each is unclear, particularly in individual vascular beds. In these experiments, we examined the role of NADPH oxidase (Nox1 and Nox2) in Ang II-induced endothelial dysfunction in the cerebral circulation. Treatment with Ang II (1.4 mg·kg
−1
·day
−1
for 7 days), but not vehicle, increased blood pressure in all groups. In wild-type (WT; C57Bl/6) mice, Ang II reduced dilation of the basilar artery to the endothelium-dependent agonist acetylcholine compared with vehicle but had no effect on responses in Nox2-deficient (Nox2
−/y
) mice. Ang II impaired responses to acetylcholine in Nox1 WT (Nox1
+/y
) and caused a small reduction in responses to acetylcholine in Nox1-deficient (Nox1
−/y
) mice. Ang II did not impair responses to the endothelium-independent agonists nitroprusside or papaverine in either group. In WT mice, Ang II increased basal and phorbol-dibutyrate-stimulated superoxide production in the cerebrovasculature, and these increases were abolished in Nox2
−/y
mice. Overall, these data suggest that Nox2 plays a relatively prominent role in mediating Ang II-induced oxidative stress and cerebral endothelial dysfunction, with a minor role for Nox1.
Details
- Title: Subtitle
- Role of Nox isoforms in angiotensin II-induced oxidative stress and endothelial dysfunction in brain
- Creators
- Sophocles Chrissobolis - Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, IowaBotond Banfi - Department of Anatomy and Cell Biology, The University of Iowa Carver College of Medicine, Iowa City, IowaChristopher G Sobey - Department of Pharmacology, Monash University, Victoria, AustraliaFrank M Faraci - Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of applied physiology (1985), Vol.113(2), pp.184-191
- DOI
- 10.1152/japplphysiol.00455.2012
- PMID
- 22628375
- PMCID
- PMC3774474
- NLM abbreviation
- J Appl Physiol (1985)
- ISSN
- 8750-7587
- eISSN
- 1522-1601
- Publisher
- American Physiological Society; Bethesda, MD
- Grant note
- HL-38901; HL-62984; NS-24621 / National Institutes of Health
- Language
- English
- Date published
- 07/15/2012
- Academic Unit
- Anatomy and Cell Biology; Cardiovascular Medicine; Neuroscience and Pharmacology; Otolaryngology; Internal Medicine
- Record Identifier
- 9984040306002771
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