Abstract
Heterozygous Cu,Zn‐Superoxide Dismutase Deficiency Reveals a Vascular Phenotype with Aging
The FASEB journal, Vol.20(5), pp.A1452-A1453
03/2006
DOI: 10.1096/fasebj.20.5.A1452-d
Abstract
The goal of the present study was to test the hypothesis that loss of a single gene for Cu,Zn‐superoxide dismutase (CuZnSOD) increases vascular superoxide and produces vascular dysfunction with aging. Responses of carotid arteries from young (6 months) and old (22–24 months of age) heterozygous CuZnSOD‐deficient (CuZnSOD+/−) mice and their wild‐type (CuZnSOD+/+) littermates were examined in vitro. Total SOD activity in aortic homogenates was reduced (P<0.05) by approximately a third in young CuZnSOD+/− mice as compared to wild‐type. Acetylcholine (ACh; an endothelium‐dependent agonist) produced similar concentration‐dependent relaxation (P>0.05) in carotid arteries from young wild‐type, young CuZnSOD+/− and old wild‐type mice. In contrast, relaxation to ACh was markedly impaired in old CuZnSOD+/− mice (eg, 100 μmol/L ACh produced 51±5 and 96±5% relaxation in vessels from old CuZnSOD+/− and old wild‐type mice, respectively). This effect was selective because relaxation to nitroprusside (an endothelium‐independent agonist) was similar (P>0.05) irrespective of age or CuZnSOD genotype. Responses to ACh in old CuZnSOD+/− mice were restored to normal following acute treatment with either tempol (a scavenger of superoxide; 1 mmol/L) or PJ34 (an inhibitor of poly‐ADP‐ribose polymerase (PARP); 3 μmol/L), suggesting that both superoxide and PARP activation contribute to endothelial dysfunction in CuZnSOD+/− mice with aging. These findings provide direct evidence that CuZnSOD expression protects endothelial function and that deficiency in a single copy of the CuZnSOD gene produces impairment of endothelial function with aging. These findings also have important implications for disease states and/or genetic polymorphisms that decrease activity of CuZnSOD.
Details
- Title: Subtitle
- Heterozygous Cu,Zn‐Superoxide Dismutase Deficiency Reveals a Vascular Phenotype with Aging
- Creators
- Sean P. Didion - Roy J. and Lucille A. Carver College of MedicineDale A. Kinzenbaw - University of IowaLaura I. Schrader - Roy J. and Lucille A. Carver College of MedicineFrank M. Faraci - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The FASEB journal, Vol.20(5), pp.A1452-A1453
- Publisher
- Federation of American Societies for Experimental Biology
- DOI
- 10.1096/fasebj.20.5.A1452-d
- ISSN
- 0892-6638
- eISSN
- 1530-6860
- Number of pages
- 2
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Internal Medicine; Cardiovascular Medicine; Neuroscience and Pharmacology
- Record Identifier
- 9984304747402771
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