Journal article
Cerebral vascular dysfunction during hypercholesterolemia
Stroke (1970), Vol.38(7), pp.2136-2141
2007
DOI: 10.1161/STROKEAHA.107.481879
PMID: 17525390
Abstract
Background and purpose: Studies of peripheral arteries in hypercholesterolemic animals suggest that increased generation of superoxide contributes to endothelial dysfunction, especially in the presence of atherosclerotic lesions. We tested the hypothesis that vasomotor function is impaired in cerebral arterioles during hypercholesterolemia through a mechanism that involves oxidative stress.
Methods: Apolipoprotein E-deficient (apoE(-/-)) mice were fed a normal or a high-fat diet for >6 months. ApoE(+/-) mice fed a normal diet were used as normocholesterolemic controls. Responses of cerebral arterioles were examined in open cranial windows in vivo in anesthetized mice.
Results: In apoE(-/-) mice, intimal area was increased only in the proximal aorta on the normal diet and also markedly increased in the distal aorta on the high-fat diet. There were no increases in intimal area in the aortas of control mice or in the cerebral arterioles in any group. The dilator response of cerebral arterioles to ACh (10 micromol/L) in control mice (26+/-4% increase in diameter) was reduced in apoE(-/-) mice on either the normal (13+/-2%) or the high-fat (13+/-3%) diet (P<0.05 vs control). NADPH (10 micromol/L), a substrate for NADPH oxidase, produced dilator responses in control mice (8+/-4%) that were significantly increased in apoE(-/-) mice on the high-fat diet (16+/-2%, P<0.05 vs control). Tempol, a superoxide scavenger, and apocynin, an inhibitor of NADPH oxidase, significantly increased vasodilator responses to ACh and decreased vasodilation to NADPH in apoE(-/-) mice on the high-fat diet. Nitroprusside produced a similar dilatation in the cerebral arterioles of all groups.
Conclusions: Hypercholesterolemia is associated with oxidative stress and endothelial dysfunction in cerebral arterioles, despite the absence of atherosclerotic lesions.
Details
- Title: Subtitle
- Cerebral vascular dysfunction during hypercholesterolemia
- Creators
- Jiro KITAYAMA - Cardiovascular Center and Departments of Internal Medicine and Pharmacology, University of Iowa Roy J. and Lucille A. Carver College of Medicine and VA Medical Center, Iowa City, Iowa, United StatesFrank M FARACI - Cardiovascular Center and Departments of Internal Medicine and Pharmacology, University of Iowa Roy J. and Lucille A. Carver College of Medicine and VA Medical Center, Iowa City, Iowa, United StatesSteven R LENTZ - Cardiovascular Center and Departments of Internal Medicine and Pharmacology, University of Iowa Roy J. and Lucille A. Carver College of Medicine and VA Medical Center, Iowa City, Iowa, United StatesDonald D HEISTAD - Cardiovascular Center and Departments of Internal Medicine and Pharmacology, University of Iowa Roy J. and Lucille A. Carver College of Medicine and VA Medical Center, Iowa City, Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Stroke (1970), Vol.38(7), pp.2136-2141
- Publisher
- Lippincott Williams & Wilkins; Hagerstown, MD
- DOI
- 10.1161/STROKEAHA.107.481879
- PMID
- 17525390
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Language
- English
- Date published
- 2007
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040264602771
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