| Reactive oxygen species-dependent hypertension in dopamine D2 receptor-deficient mice. | |
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MedLine Citation:
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PMID: 17190875 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dysfunction of D2-like receptors has been reported in essential hypertension. Disruption of D2R in mice (D2-/-) results in high blood pressure, and several D2R polymorphisms are associated with decreased D2R expression. Because D2R agonists have antioxidant activity, we hypothesized that increased blood pressure in D2-/- is related to increased oxidative stress. D2-/- mice had increased urinary excretion of 8-isoprostane, a parameter of oxidative stress; increased activity of reduced nicotinamide-adenine dinucleotide phosphate oxidase in renal cortex; increased expression of the reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits Nox1, Nox2, and Nox4; and decreased expression of the antioxidant enzyme heme-oxygenase-2 in the kidneys, suggesting that regulation of reactive oxygen species (ROS) production by D2R involves both pro-oxidant and antioxidant systems. Apocynin, a reduced nicotinamide-adenine dinucleotide phosphate oxidase inhibitor, or hemin, an inducer of heme oxigenase-1, normalized the blood pressure in D2-/- mice. Because D2Rs in the adrenal gland are implicated in aldosterone regulation, we evaluated whether alterations in aldosterone secretion contribute to ROS production in this model. Urinary aldosterone was increased in D2-/- mice and its response to a high-sodium diet was impaired. Spirolactone normalized the blood pressure in D2-/- mice and the renal expression of Nox1 and Nox4, indicating that the increased blood pressure and ROS production are, in part, mediated by impaired aldosterone regulation. However, spironolactone did not normalize the excretion of 8-isoprostane and had no effect on expression of Nox2 or heme-oxygenase-2. Our results show that the D2R is involved in the regulation of ROS production and that, by direct and indirect mechanisms, altered D2R function may result in ROS-dependent hypertension. |
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Authors:
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Ines Armando; Xiaoyan Wang; Van Anthony M Villar; John E Jones; Laureano D Asico; Crisanto Escano; Pedro A Jose |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2006-12-26 |
Journal Detail:
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Title: Hypertension Volume: 49 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2007 Mar |
Date Detail:
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Created Date: 2007-02-16 Completed Date: 2007-03-06 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 672-8 Citation Subset: IM |
Affiliation:
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Department of Pediatrics and Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20057, USA. ma383@georgetown.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aldosterone
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metabolism Animals Antioxidants / metabolism Blood Pressure / physiology* Hypertension / metabolism, physiopathology* Mice Oxidants / metabolism Oxidative Stress* Reactive Oxygen Species / metabolism* Receptors, Dopamine D2 / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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DK39308/DK/NIDDK NIH HHS; DK52612/DK/NIDDK NIH HHS; HL074940/HL/NHLBI NIH HHS; HL23081/HL/NHLBI NIH HHS; HL68686/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Oxidants; 0/Reactive Oxygen Species; 0/Receptors, Dopamine D2; 52-39-1/Aldosterone |
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