Hypertrophy of cerebral arterioles in mice deficient in expression of the gene for CuZn superoxide dismutase

Gary L BAUMBACH; Sean P DIDION; Frank M FARACI

doi:10.1161/01.STR.0000227236.84546.5a

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Hypertrophy of cerebral arterioles in mice deficient in expression of the gene for CuZn superoxide dismutase

Journal article

Open access

Peer reviewed

Hypertrophy of cerebral arterioles in mice deficient in expression of the gene for CuZn superoxide dismutase

Gary L BAUMBACH, Sean P DIDION and Frank M FARACI

Stroke (1970), Vol.37(7), pp.1850-1855

2006

DOI: 10.1161/01.STR.0000227236.84546.5a

PMID: 16763183

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Abstract

Background and purpose: Reactive oxygen species are believed to be an important determinant of vascular growth. We examined effects of genetic deficiency of copper-zinc superoxide dismutase (CuZnSOD; SOD1) on structure and function of cerebral arterioles. Methods: Systemic arterial pressure (SAP) and cross-sectional area of the vessel wall (CSA) and superoxide (O2-) levels (relative fluorescence of ethidium [ETH]) were examined in maximally dilated cerebral arterioles in mice with targeted disruption of one (+/-) or both (-/-) genes encoding CuZnSOD. Wild-type littermates served as controls. Vasodilator responses were tested in separate groups of mice. Results: CSA and ETH were significantly increased (P<0.05) in both CuZnSOD+/- and CuZnSOD-/- mice (CSA=435+/-24 and 541+/-48 microm2; ETH=18+/-1 and 34+/-2%) compared with wild-type mice (CSA=327+/-28 microm2; ETH=6%). Furthermore, the increases in CSA and ETH relative to wild-type mice were significantly greater (P<0.05) in CuZnSOD-/- mice than in CuZnSOD+/- mice (CSA=108 versus 214 microm2; ETH=12 versus 28%). In addition, dilatation of cerebral arterioles in response to acetylcholine, but not nitroprusside, was reduced by approximately 25% in CuZnSOD+/- (P<0.075) and 50% in CuZnSOD-/- mice (P<0.05) compared with wild-type mice. Conclusions: Cerebral arterioles in CuZnSOD+/- and CuZnSOD-/- mice undergo marked hypertrophy. These findings provide the first direct evidence in any blood vessel that CuZnSOD normally inhibits vascular hypertrophy suggesting that CuZnSOD plays a major role in regulation of cerebral vascular growth. The findings also suggest a gene dosing effect of CuZnSOD for increases in O2-, induction of cerebral vascular hypertrophy and impaired endothelium-dependent dilatation.

Biotechnology

Neurology

Gene Therapy

Fundamental and applied biological sciences. Psychology

Health. Pharmaceutical industry

Industrial applications and implications. Economical aspects

Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy

Biological and medical sciences

Vascular diseases and vascular malformations of the nervous system

Medical sciences

Nervous system (semeiology, syndromes)

Details

Title: Subtitle: Hypertrophy of cerebral arterioles in mice deficient in expression of the gene for CuZn superoxide dismutase
Creators: Gary L BAUMBACH - Department of Pathology, University of Iowa College of Medicine & Cardiovascular Center, Iowa City, IA, United States
Sean P DIDION - Department of Internal Medicine, University of Iowa College of Medicine & Cardiovascular Center, Iowa City, IA, United States
Frank M FARACI - Department of Internal Medicine, University of Iowa College of Medicine & Cardiovascular Center, Iowa City, IA, United States
Resource Type: Journal article
Publication Details: Stroke (1970), Vol.37(7), pp.1850-1855
Publisher: Lippincott Williams & Wilkins; Hagerstown, MD
DOI: 10.1161/01.STR.0000227236.84546.5a
PMID: 16763183
ISSN: 0039-2499
eISSN: 1524-4628
Language: English
Date published: 2006
Academic Unit: Pathology; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040496402771

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