Angiotensin II produces superoxide-mediated impairment of endothelial function in cerebral arterioles

Sean P Didion; Frank M Faraci

doi:10.1161/01.STR.0000081225.46324.AA

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Angiotensin II produces superoxide-mediated impairment of endothelial function in cerebral arterioles

Journal article

Open access

Peer reviewed

Angiotensin II produces superoxide-mediated impairment of endothelial function in cerebral arterioles

Sean P Didion and Frank M Faraci

Stroke (1970), Vol.34(8), pp.2038-2042

08/2003

DOI: 10.1161/01.STR.0000081225.46324.AA

PMID: 12829858

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Abstract

Angiotensin II (Ang II) produces oxidative stress in vascular cells in culture and in extracranial conduit arteries. The goal of this study was to examine the hypothesis that Ang II produces superoxide-mediated impairment of endothelial function in cerebral microvessels. Diameter of cerebral arterioles (baseline diameter=104+/-3 microm) was measured with the use of a closed cranial window in anesthetized rabbits. Topical application of Ang II was used to avoid effects on arterial pressure. Ang II (0.1 to 1 micromol/L for 2 hours) had no effect on baseline diameter (change in diameter of -3+/-2% in response to 1 micromol/L Ang II) but produced concentration-dependent inhibition of vasodilatation to the endothelium-dependent agonist bradykinin. For example, 1 micromol/L Ang II inhibited responses to 1 nmol/L bradykinin by almost 80%. These inhibitory effects of Ang II were prevented by the superoxide scavenger 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron; 10 mmol/L) or diphenylene iodonium (DPI; 3 micromol/L), an inhibitor of NAD(P)H oxidase. Ang II did not inhibit vasodilatation in response to nitroprusside, an endothelium-independent vasodilator. These findings are the first evidence that local Ang II produces superoxide-mediated vascular dysfunction in cerebral microvessels. The results with DPI suggest that the source of superoxide may be an NAD(P)H oxidase.

Arterioles - physiology

Free Radical Scavengers - pharmacology

Cerebral Cortex - blood supply

Endothelium, Vascular - drug effects

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt - pharmacology

Microcirculation - drug effects

Endothelium, Vascular - physiology

Microcirculation - physiology

Superoxides - metabolism

Blood Pressure - drug effects

Blood Pressure - physiology

Cerebral Cortex - drug effects

Nitric Oxide Donors - pharmacology

Bradykinin - pharmacology

Rabbits

Angiotensin II - pharmacology

NADPH Oxidases - antagonists & inhibitors

Enzyme Inhibitors - pharmacology

Pia Mater - blood supply

Bradykinin - antagonists & inhibitors

Vascular Patency - drug effects

Arterioles - drug effects

Animals

Cerebral Cortex - physiology

Vasodilation - drug effects

Administration, Topical

Details

Title: Subtitle: Angiotensin II produces superoxide-mediated impairment of endothelial function in cerebral arterioles
Creators: Sean P Didion - Department of Internal Medicine, Cardiovascular Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242-1081, USA
Frank M Faraci
Resource Type: Journal article
Publication Details: Stroke (1970), Vol.34(8), pp.2038-2042
DOI: 10.1161/01.STR.0000081225.46324.AA
PMID: 12829858
NLM abbreviation: Stroke
ISSN: 0039-2499
eISSN: 1524-4628
Publisher: United States
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: 08/2003
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040469602771

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