Critical role for CuZn-superoxide dismutase in preventing angiotensin II-induced endothelial dysfunction

Sean P Didion; Dale A Kinzenbaw; Frank M Faraci

doi:10.1161/01.HYP.0000187532.80697.15

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Critical role for CuZn-superoxide dismutase in preventing angiotensin II-induced endothelial dysfunction

Journal article

Open access

Peer reviewed

Critical role for CuZn-superoxide dismutase in preventing angiotensin II-induced endothelial dysfunction

Sean P Didion, Dale A Kinzenbaw and Frank M Faraci

Hypertension (Dallas, Tex. 1979), Vol.46(5), pp.1147-1153

11/2005

DOI: 10.1161/01.HYP.0000187532.80697.15

PMID: 16216984

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Abstract

The goal of the present study was to test the hypothesis that the CuZn isoform of superoxide dismutase (CuZnSOD) protects against angiotensin II (Ang II)-induced endothelial dysfunction. Vascular responses of carotid arteries from control, CuZnSOD-deficient (CuZnSOD(+/-)), and CuZnSOD transgenic mice were examined in vitro after overnight incubation with either vehicle or Ang II (1 or 10 nmol/L). In control mice, acetylcholine produced concentration-dependent relaxation that was not affected by 1 nmol/L Ang II. In contrast, relaxation to acetylcholine in arteries from CuZnSOD+/- mice was markedly and selectively attenuated after incubation with 1 nmol/L Ang II (eg, 100 micromol/L acetylcholine produced 93+/-6% and 44+/-15% relaxation in vehicle- and Ang II-treated arteries, respectively). A higher concentration of Ang II (10 nmol/L) selectively impaired relaxation to acetylcholine in arteries from control mice (eg, 100 micromol/L acetylcholine produced 96+/-4% and 45+/-7% relaxation in vehicle- and Ang II-treated vessels, respectively). In contrast, 10 nmol/L Ang II had no effect on responses to acetylcholine in carotid arteries from CuZnSOD transgenic mice (or in control mice treated with the superoxide scavenger Tiron [1 mmol/L]). Superoxide levels in control mice were higher in aorta treated with Ang II than with vehicle and were markedly reduced in CuZnSOD transgenic mice. These findings provide the first direct evidence that CuZnSOD limits Ang II-mediated impairment of endothelial function and that loss of 1 copy of the CuZnSOD gene is sufficient to enhance Ang II-induced vascular dysfunction.

Carotid Arteries - drug effects

Angiotensin II - pharmacology

Superoxide Dismutase - genetics

Vasodilator Agents - pharmacology

Angiotensin II - administration & dosage

Acetylcholine - pharmacology

Mice, Inbred C57BL

Endothelium, Vascular - physiopathology

Angiotensin II - antagonists & inhibitors

Endothelium, Vascular - drug effects

Male

Mice, Transgenic

Gene Dosage

Dose-Response Relationship, Drug

Animals

Osmolar Concentration

Carotid Arteries - physiopathology

Superoxide Dismutase - physiology

Mice

Vasodilation - physiology

Details

Title: Subtitle: Critical role for CuZn-superoxide dismutase in preventing angiotensin II-induced endothelial dysfunction
Creators: Sean P Didion - Department of Internal Medicine, Cardiovascular Center, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. sean-didion@uiowa.edu
Dale A Kinzenbaw
Frank M Faraci
Resource Type: Journal article
Publication Details: Hypertension (Dallas, Tex. 1979), Vol.46(5), pp.1147-1153
Publisher: United States
DOI: 10.1161/01.HYP.0000187532.80697.15
PMID: 16216984
ISSN: 0194-911X
eISSN: 1524-4563
Grant note: HL-38901 / NHLBI NIH HHS NS-24621 / NINDS NIH HHS DK-25295 / NIDDK NIH HHS HL-62984 / NHLBI NIH HHS
Language: English
Date published: 11/2005
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040483202771

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