Vascular Oxidative Stress and Endothelial Dysfunction in Patients With Chronic Heart Failure
Top Cited Papers
- 10 December 2002
- journal article
- clinical trial
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 106 (24), 3073-3078
- https://doi.org/10.1161/01.cir.0000041431.57222.af
Abstract
Background— Impaired flow-dependent, endothelium-mediated vasodilation (FDD) in patients with chronic heart failure (CHF) results, at least in part, from accelerated degradation of nitric oxide by oxygen radicals. The mechanisms leading to increased vascular radical formation, however, remain unclear. Therefore, we determined endothelium-bound activities of extracellular superoxide dismutase (ecSOD), a major vascular antioxidant enzyme, and xanthine-oxidase, a potent radical producing enzyme, and their relation to FDD in patients with CHF. Methods and Results— ecSOD and xanthine-oxidase activities, released from endothelium into plasma by heparin bolus injection, were determined in 14 patients with CHF and 10 control subjects. FDD of the radial artery was measured using high-resolution ultrasound and was assessed before and after administration of the antioxidant vitamin C (25 mg/min; IA). In patients with CHF, endothelium-bound ecSOD activity was substantially reduced (5.0±0.7 versus 14.4±2.6 U · mL −1 · min −1 ; P 200% (38±10 versus 12±4 nmol O 2 ·− · μL −1 ; P r =−0.35) in patients with CHF. In patients with low ecSOD and high xanthine-oxidase activity, a greater benefit of vitamin C on FDD was observed, ie, the portion of FDD inhibited by radicals correlated negatively with ecSOD ( r =−0.71) but positively with xanthine-oxidase ( r =0.75). Conclusions— These results demonstrate that both increased xanthine-oxidase and reduced ecSOD activity are closely associated with increased vascular oxidative stress in patients with CHF. This loss of vascular oxidative balance likely represents a novel mechanism contributing to endothelial dysfunction in CHF.Keywords
This publication has 33 references indexed in Scilit:
- Effects of Xanthine Oxidase Inhibition With Allopurinol on Endothelial Function and Peripheral Blood Flow in Hyperuricemic Patients With Chronic Heart FailureCirculation, 2002
- Enhanced Expression and Activity of Xanthine Oxidoreductase in the Failing HeartJournal of Molecular and Cellular Cardiology, 2000
- Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise trainingJCI Insight, 2000
- Immunoaffinity localization of the enzyme xanthine oxidase on the outside surface of the endothelial cell plasma membraneSurgery, 1998
- Spin Trapping of Superoxide Radicals and Peroxynitrite by 1-Hydroxy-3-carboxy-pyrrolidine and 1-Hydroxy-2,2,6,6-tetramethyl-4-oxo-piperidine and the Stability of Corresponding Nitroxyl Radicals Towards Biological ReductantsBiochemical and Biophysical Research Communications, 1997
- Endothelial dysfunction: Clinical implicationsProgress in Cardiovascular Diseases, 1997
- Xanthine oxidase activity in the circulation of rats following hemorrhagic shockFree Radical Biology & Medicine, 1993
- Endothelial function in chronic congestive heart failureThe American Journal of Cardiology, 1992
- Extracellular superoxide dismutase in human tissues and human cell lines.JCI Insight, 1984
- Alterations in vasomotor tone in congestive heart failureProgress in Cardiovascular Diseases, 1982