Journal article
Endothelin-1 stimulates arterial VCAM-1 expression via NADPH oxidase-derived superoxide in mineralocorticoid hypertension
Hypertension (Dallas, Tex. 1979), Vol.42(5), pp.997-1003
2003
DOI: 10.1161/01.HYP.0000095980.43859.59
PMID: 14517226
Abstract
Although hypertension is a major risk factor for atherosclerosis, its underlying mechanisms remain to be delineated. We have recently reported that both endothelin-1 (ET-1) and vascular cellular adhesion molecule-1 (VCAM-1) levels, key early markers of atherosclerosis, are significantly elevated in carotid arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats, a model known for its suppressed plasma renin levels. This study tested the hypothesis that ET-1 augments arterial VCAM-1 expression through NADPH oxidase-derived superoxide (O2−). Carotid arteries of DOCA-salt or sham-operated rats were transduced ex vivo with extracellular superoxide dismutase (EC-SOD), dominant negative HA-tagged N17Rac1 that inhibits Rac1, the small GTPase component of NADPH oxidase, or β-galactosidase (β-gal) reporter gene (5×1010 plaque formation units [pfu]/mL), and the effect of transgene expression on O2− and VCAM-1 levels was assayed 24 hours afterward. The arterial activity of NADPH oxidase but not xanthine oxidase was significantly higher in DOCA-salt than in sham rats, which was abolished by the selective ETA receptor antagonist ABT-627 (3×10−8 mol/L), NADPH oxidase inhibitor apocynin (10−4 mol/L), or dominant negative Rac1 gene transfer. The levels of O2− and VCAM-1 were significantly increased in arteries of DOCA-salt rats, an effect that was ameliorated after EC-SOD or dominant negative Rac1 but not β-gal reporter gene transfer. ABT-627 and apocynin also significantly reduced elevated VCAM-1 levels in ET-1-treated arteries of normal rats and arteries of DOCA-salt rats. The results of this study indicate that ET-1 stimulates arterial VCAM-1 expression by producing O2− from an ETA receptor/NADPH oxidase pathway in low-renin mineralocorticoid hypertension.
Details
- Title: Subtitle
- Endothelin-1 stimulates arterial VCAM-1 expression via NADPH oxidase-derived superoxide in mineralocorticoid hypertension
- Creators
- Lixin Li - Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, United StatesYi Chu - Department of Medicine, University of Iowa, Iowa City, United StatesGregory D FINK - Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, United StatesJohn F ENGELHARDT - Department of Medicine, University of Iowa, Iowa City, United StatesDonald D HEISTAD - Department of Medicine, University of Iowa, Iowa City, United StatesAlex F CHEN - Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, United States
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.42(5), pp.997-1003
- Publisher
- Lippincott; Philadelphia, PA; Hagerstown, MD
- DOI
- 10.1161/01.HYP.0000095980.43859.59
- PMID
- 14517226
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 2003
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Cardiovascular Medicine; Radiation Oncology; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984040243502771
Metrics
24 Record Views