Abstract
Endothelial Dysfunction in Cerebral Arterioles in a Model of Diet‐Induced Obesity and Type II Diabetes: Role of Superoxide and NAD(P)H Oxidase
The FASEB journal, Vol.20(4), pp.A295-A295
03/2006
DOI: 10.1096/fasebj.20.4.A295
Abstract
The goal of this study was to characterize responses in the cerebral circulation in a mouse model of diet‐induced obesity and type II diabetes and to examine the mechanisms involved. Diameter of cerebral arterioles (31±1 μm; mean±SE) was measured using a cranial window preparation in anesthetized C57Bl/6 and gp91phox‐deficient mice fed either a control (10% kcal fat) or a high‐fat (45% kcal fat) diet for 12 weeks. Blood glucose levels were higher in high‐fat fed mice compared to controls (160±10 vs. 120±16 mg/dl, respectively). Dilatation in response to acetylcholine (ACh; 1 and 10 μmol/L), but not to nitroprusside (NP), was markedly reduced (P<0.05) in C57Bl/6 mice fed a high‐fat diet (eg, 10 μmol/L ACh produced 33±4 and 18±1% dilatation in control and high‐fat fed mice, respectively). Responses to ACh in high‐fat fed C57Bl/6 mice were restored toward normal by tempol (a scavenger of superoxide; 1 mmol/L). Responses to ACh and NP in high‐fat fed gp91phox‐deficient were similar (P>0.05) to that observed in C57Bl/6 mice fed a control diet (eg, 10 μmol/L ACh produced 33±4 and 28±1% dilation in high‐fat fed gp91phox‐deficient mice compared to that in control‐diet fed C57Bl/6 mice, respectively). These findings provide the first evidence that endothelium‐dependent responses of cerebral vessels are markedly impaired in a mouse model of diet‐induced obesity and type II diabetes. Pharmacological and genetic evidence implicate a major role for NAD(P)H oxidase‐derived superoxide in impairment of cerebral microvessels in response to a high‐fat diet.
Details
- Title: Subtitle
- Endothelial Dysfunction in Cerebral Arterioles in a Model of Diet‐Induced Obesity and Type II Diabetes: Role of Superoxide and NAD(P)H Oxidase
- Creators
- Sean P. Didion - Roy J. and Lucille A. Carver College of MedicineCynthia M. Lynch - Roy J. and Lucille A. Carver College of MedicineFrank M. Faraci - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.20(4), pp.A295-A295
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.20.4.A295
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 1
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984304001902771
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