Effect of aging, MnSOD deficiency, and genetic background on endothelial function : Evidence for MnSOD haploinsufficiency

Kathryn A BROWN; Sean P DIDION; Jon J ANDRESEN; Frank M FARACI

doi:10.1161/ATVBAHA.107.146852

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Effect of aging, MnSOD deficiency, and genetic background on endothelial function : Evidence for MnSOD haploinsufficiency

Kathryn A BROWN, Sean P DIDION, Jon J ANDRESEN and Frank M FARACI

Arteriosclerosis, thrombosis, and vascular biology, Vol.27(9), pp.1941-1946

2007

DOI: 10.1161/ATVBAHA.107.146852

PMID: 17556650

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Abstract

Objective: The goal of this study was to compare vascular function, superoxide levels, and MnSOD protein expression in young (4 to 7 months) and old (22 to 24 months) MnSOD+/+ and MnSOD-deficient (MnSOD+/-) mice. Methods and results: Relaxation of aorta in vitro to the endothelium-dependent dilator acetylcholine (ACh) was similar in young MnSOD+/+ (n=9) and young MnSOD+/- (n=6) mice. This response was impaired in old MnSOD+/+ (n=8) mice and old MnSOD+/- mice (n=14), with dysfunction being greater in old MnSOD-deficient mice (eg, 100 micromol/L ACh produced 77+/-3% [mean+/-SE], 77+/-3%, 70+/-4%, and 57+/-4% relaxation in young MnSOD+/+, young MnSOD+/-, old MnSOD+/+, and old MnSOD+/- mice, respectively). The endothelial dysfunction was similar in mice on both C57BL/6 and CD-1 genetic backgrounds. In contrast to ACh, responses to the endothelium-independent dilator sodium nitroprusside were enhanced in old MnSOD+/+ and MnSOD+/- mice compared with both groups of young mice (P<0.05). Superoxide levels, as measured using lucigenin-enhanced chemiluminescence, were increased more than 2-fold in old MnSOD+/- mice compared with old MnSOD+/+ and young mice (P<0.05). Conclusions: These data provide the first direct evidence that MnSOD haploinsufficiency results in increased vascular oxidative stress and endothelial dysfunction with aging.

Cardiovascular System

Cardiology. Vascular system

Investigative techniques, diagnostic techniques (general aspects)

Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous

Atherosclerosis (general aspects, experimental research)

Pharmacology. Drug treatments

Biological and medical sciences

Investigative techniques of hemodynamics

Medical sciences

Vasodilator agents. Cerebral vasodilators

Blood and lymphatic vessels

Details

Title: Subtitle: Effect of aging, MnSOD deficiency, and genetic background on endothelial function : Evidence for MnSOD haploinsufficiency
Creators: Kathryn A BROWN - Department of Pharmacology, Cardiovascular Center, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, United States
Sean P DIDION - Department of Internal Medicine, Cardiovascular Center, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, United States
Jon J ANDRESEN - Department of Internal Medicine, Cardiovascular Center, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, United States
Frank M FARACI - Department of Pharmacology, Cardiovascular Center, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, United States
Resource Type: Journal article
Publication Details: Arteriosclerosis, thrombosis, and vascular biology, Vol.27(9), pp.1941-1946
Publisher: Lippincott; Philadelphia, PA; Hagerstown, MD
DOI: 10.1161/ATVBAHA.107.146852
PMID: 17556650
ISSN: 1079-5642
eISSN: 1524-4636
Language: English
Date published: 2007
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040481002771

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