Superoxide contributes to vascular dysfunction in mice that express human renin and angiotensinogen

Sean P Didion; Michael J Ryan; Gary L Baumbach; Curt D Sigmund; Frank M Faraci

doi:10.1152/ajpheart.00079.2002

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Superoxide contributes to vascular dysfunction in mice that express human renin and angiotensinogen

Journal article

Peer reviewed

Superoxide contributes to vascular dysfunction in mice that express human renin and angiotensinogen

Sean P Didion, Michael J Ryan, Gary L Baumbach, Curt D Sigmund and Frank M Faraci

American journal of physiology. Heart and circulatory physiology, Vol.283(4), pp.H1569-1576

10/2002

DOI: 10.1152/ajpheart.00079.2002

PMID: 12234811

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Abstract

This study examined vascular function and the role of superoxide in mice that chronically express human renin (R+) and human angiotensinogen (A+). Responses of aortas from R+/A+ mice and from their normotensive littermates (RA- mice) were examined in vitro. Endothelium-dependent relaxation to acetylcholine was impaired in vessels from R+/A+ mice (e.g., maximal relaxation to 100 microM acetylcholine was 45 +/- 5% and 65 +/- 3% in R+/A+ and RA- mice, respectively; P < 0.05). Relaxation was also impaired to the endothelium-independent dilators authentic nitric oxide and nitroprusside in vessels from R+/A+ mice. Maximal vasorelaxation to the endothelium-independent, non-nitric oxide dilator papaverine was similar in R+/A+ and RA- mice. Incubation of vessels from R+/A+ mice with Tiron (1 mM), a superoxide scavenger, improved relaxation to acetylcholine, nitric oxide, and nitroprusside. In contrast, incubation with diethyldithiocarbamate (1 mM), an inhibitor of copper-containing SODs, reduced acetylcholine- and nitroprusside-induced relaxation in vessels from both R+/A+ and RA- mice. Basal superoxide levels, measured with lucigenin-enhanced chemiluminescence (5 microM lucigenin) and hydroethidine-based fluorescent confocal microscopy, were higher in vessels from R+/A+ mice and were Tiron and polyethylene glycol-SOD sensitive. These results suggest that increased superoxide contributes to impaired nitric oxide-mediated relaxation in this genetic model of chronic angiotensin II-dependent hypertension.

Reactive Oxygen Species - metabolism

Vasodilator Agents - pharmacology

Acetylcholine - pharmacology

Humans

Mice, Transgenic

Papaverine - pharmacology

Chelating Agents - pharmacology

Luminescent Measurements

Hypertension - physiopathology

Hypertension - metabolism

Angiotensinogen - genetics

Renin - genetics

Animals

Ditiocarb - pharmacology

Superoxides - metabolism

Blood Pressure - drug effects

Blood Pressure - physiology

Mice

Vasodilation - drug effects

Vasodilation - physiology

Nitric Oxide - metabolism

Aorta - physiology

Superoxide Dismutase - metabolism

Details

Title: Subtitle: Superoxide contributes to vascular dysfunction in mice that express human renin and angiotensinogen
Creators: Sean P Didion - Department of Internal Medicine, Cardiovascular Center, University of Iowa College of Medicine, Iowa City 52242, USA
Michael J Ryan
Gary L Baumbach
Curt D Sigmund
Frank M Faraci
Resource Type: Journal article
Publication Details: American journal of physiology. Heart and circulatory physiology, Vol.283(4), pp.H1569-1576
Publisher: United States
DOI: 10.1152/ajpheart.00079.2002
PMID: 12234811
ISSN: 0363-6135
eISSN: 1522-1539
Grant note: HL-48058 / NHLBI NIH HHS HL-10425 / NHLBI NIH HHS HL-10237 / NHLBI NIH HHS HL-38901 / NHLBI NIH HHS NS-24621 / NINDS NIH HHS HL-61446 / NHLBI NIH HHS HL-62984 / NHLBI NIH HHS HL-55006 / NHLBI NIH HHS
Language: English
Date published: 10/2002
Academic Unit: Molecular Physiology and Biophysics; Pathology; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040216502771

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