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- ISSN
- 0009-7330
- eISSN
- 1524-4571
- DOI
- 10.1161/CIRCRESAHA.109.214601
- pmid
- 20448215
- Publisher site
- See Article on Publisher Site
Abstract
Therapeutic Targeting of Mitochondrial Superoxide in Hypertension Anna E. Dikalova, Alfiya T. Bikineyeva, Klaudia Budzyn, Rafal R. Nazarewicz, Louise McCann, William Lewis, David G. Harrison, Sergey I. Dikalov Rationale: Superoxide (O ) has been implicated in the pathogenesis of many human diseases including hyperten- sion; however, commonly used antioxidants have proven ineffective in clinical trials. It is possible that these agents are not adequately delivered to the subcellular sites of superoxide production. Objective: Because the mitochondria are important sources of reactive oxygen species, we postulated that mitochondrial targeting of superoxide scavenging would have therapeutic benefit. Methods and Results: In this study, we found that the hormone angiotensin (Ang II) increased endothelial mitochondrial superoxide production. Treatment with the mitochondria-targeted antioxidant mitoTEMPO . . decreased mitochondrial O , inhibited the total cellular O , reduced cellular NADPH oxidase activity, and 2 2 restored the level of bioavailable NO. These effects were mimicked by overexpressing the mitochondrial MnSOD (SOD2), whereas SOD2 depletion with small interfering RNA increased both basal and Ang II–stimulated cellular O . Treatment of mice in vivo with mitoTEMPO attenuated hypertension when given at the onset of Ang II infusion and decreased blood pressure by 30 mm Hg following
Journal
Circulation Research – Wolters Kluwer Health
Published: Jul 1, 2010