Journal article
Paradoxical Activation of Endothelial Nitric Oxide Synthase by NADPH Oxidase
Arteriosclerosis, thrombosis, and vascular biology, Vol.28(9), pp.1627-1633
09/2008
DOI: 10.1161/ATVBAHA.108.168278
PMCID: PMC2771553
PMID: 18556569
Abstract
Objectives—
Increased formation of reactive oxygen species (ROS) has been identified as a causative factor in endothelial dysfunction by reducing NO bioavailability and uncoupling endothelial nitric oxide synthase (eNOS). However, the specific contribution of ROS to endothelial function is not well understood.
Methods and Results—
A major source of intracellular ROS is the NADPH oxidase (Nox) family of enzymes. The goal of the current study was to directly assess the contribution of NADPH oxidase derived superoxide to eNOS function by expressing Nox5, a single gene product that constitutively produces superoxide within cells. Paradoxically, we found that instead of inhibiting eNOS, coexpression of Nox5 increased NO release from both bovine and human endothelial cells. To establish the functional significance of this observation in intact blood vessels, the endothelium of mouse aorta was transduced with Nox5 or control adenoviruses. Nox5 potently inhibited Ach-induced relaxation and potentiated contractile responses to phenylephrine. In precontracted aortae, acute exposure to superoxide dismutase induced significant vascular relaxation in vessels exposed to Nox5 versus control and unmasked the ability of Nox5 to activate eNOS in blood vessel endothelium.
Conclusions—
These findings suggest that ROS inhibit eNOS function via consumption of NO rather than direct inhibition of enzymatic activity.
Details
- Title: Subtitle
- Paradoxical Activation of Endothelial Nitric Oxide Synthase by NADPH Oxidase
- Creators
- Qian Zhang - Prevention InstitutePulkit Malik - Prevention InstituteDeepesh Pandey - Prevention InstituteSonali Gupta - Prevention InstituteDavin Jagnandan - Prevention InstituteEric Belin de Chantemele - From the Departments of Pharmacology, Physiology, and the Vascular Biology Center, Medical College of Georgia, AugustaBotond Banfi - Prevention InstituteMario B. Marrero - Augusta UniversityR. Daniel Rudic - Pharmacology and ToxicologyDavid W. Stepp - Augusta UniversityDavid J.R. Fulton - From the Departments of Pharmacology, Physiology, and the Vascular Biology Center, Medical College of Georgia, Augusta
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.28(9), pp.1627-1633
- DOI
- 10.1161/ATVBAHA.108.168278
- PMID
- 18556569
- PMCID
- PMC2771553
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Language
- English
- Date published
- 09/2008
- Academic Unit
- Anatomy and Cell Biology; Otolaryngology; Internal Medicine
- Record Identifier
- 9984284451502771
Metrics
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