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Molecular Mechanisms of Angiotensin II–Mediated Mitochondrial Dysfunction Linking Mitochondrial Oxidative Damage and Vascular Endothelial Dysfunction

Molecular Mechanisms of Angiotensin II–Mediated Mitochondrial Dysfunction Linking... Integrative Physiology Molecular Mechanisms of Angiotensin II–Mediated Mitochondrial Dysfunction Linking Mitochondrial Oxidative Damage and Vascular Endothelial Dysfunction Abdulrahman K. Doughan, David G. Harrison, Sergey I. Dikalov Abstract—Mitochondrial dysfunction is a prominent feature of most cardiovascular diseases. Angiotensin (Ang) II is an important stimulus for atherogenesis and hypertension; however, its effects on mitochondrial function remain unknown. We hypothesized that Ang II could induce mitochondrial oxidative damage that in turn might decrease endothelial nitric oxide (NO˙) bioavailability and promote vascular oxidative stress. The effect of Ang II on mitochondrial ROS, mitochondrial respiration, membrane potential, glutathione, and endothelial NO˙ was studied in isolated mitochondria and intact bovine aortic endothelial cells using electron spin resonance, dihydroethidium high-performance liquid chromatography – based assay, Amplex Red and cationic dye fluorescence. Ang II significantly increased mitochondrial H O production. This increase was blocked by preincubation of intact cells with apocynin (NADPH oxidase inhibitor), 2 2 uric acid (scavenger of peroxynitrite), chelerythrine (protein kinase C inhibitor), N -nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), 5-hydroxydecanoate (mitochondrial ATP-sensitive potassium channels inhibitor), or gliben- phox clamide. Depletion of p22 subunit of NADPH oxidase with small interfering RNA also inhibited Ang II–mediated mitochondrial ROS production. Ang II depleted mitochondrial glutathione, http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Circulation Research Wolters Kluwer Health

Molecular Mechanisms of Angiotensin II–Mediated Mitochondrial Dysfunction Linking Mitochondrial Oxidative Damage and Vascular Endothelial Dysfunction

Dikalov, Sergey I.
Circulation Research , Volume 102 (4) – Feb 1, 2008
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References (46)

ISSN
0009-7330
eISSN
1524-4571
DOI
10.1161/CIRCRESAHA.107.162800
pmid
18096818
Publisher site
See Article on Publisher Site

Abstract

Integrative Physiology Molecular Mechanisms of Angiotensin II–Mediated Mitochondrial Dysfunction Linking Mitochondrial Oxidative Damage and Vascular Endothelial Dysfunction Abdulrahman K. Doughan, David G. Harrison, Sergey I. Dikalov Abstract—Mitochondrial dysfunction is a prominent feature of most cardiovascular diseases. Angiotensin (Ang) II is an important stimulus for atherogenesis and hypertension; however, its effects on mitochondrial function remain unknown. We hypothesized that Ang II could induce mitochondrial oxidative damage that in turn might decrease endothelial nitric oxide (NO˙) bioavailability and promote vascular oxidative stress. The effect of Ang II on mitochondrial ROS, mitochondrial respiration, membrane potential, glutathione, and endothelial NO˙ was studied in isolated mitochondria and intact bovine aortic endothelial cells using electron spin resonance, dihydroethidium high-performance liquid chromatography – based assay, Amplex Red and cationic dye fluorescence. Ang II significantly increased mitochondrial H O production. This increase was blocked by preincubation of intact cells with apocynin (NADPH oxidase inhibitor), 2 2 uric acid (scavenger of peroxynitrite), chelerythrine (protein kinase C inhibitor), N -nitro-L-arginine methyl ester (nitric oxide synthase inhibitor), 5-hydroxydecanoate (mitochondrial ATP-sensitive potassium channels inhibitor), or gliben- phox clamide. Depletion of p22 subunit of NADPH oxidase with small interfering RNA also inhibited Ang II–mediated mitochondrial ROS production. Ang II depleted mitochondrial glutathione,

Journal

Circulation Research – Wolters Kluwer Health

Published: Feb 1, 2008

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