| Role of the NADPH oxidases in the subfornical organ in angiotensin II-induced hypertension. | |
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MedLine Citation:
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PMID: 23248154 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Reactive oxygen species and the NADPH oxidases contribute to hypertension via mechanisms that remain undefined. Reactive oxygen species produced in the central nervous system have been proposed to promote sympathetic outflow, inflammation, and hypertension, but the contribution of the NADPH oxidases to these processes in chronic hypertension is uncertain. We therefore sought to identify how NADPH oxidases in the subfornical organ (SFO) of the brain regulate blood pressure and vascular inflammation during sustained hypertension. We produced mice with loxP sites flanking the coding region of the NADPH oxidase docking subunit p22(phox). SFO-targeted injections of an adenovirus encoding cre-recombinase markedly diminished p22(phox), Nox2, and Nox4 mRNA in the SFO, as compared with a control adenovirus encoding red-fluorescent protein injection. Increased superoxide production in the SFO by chronic angiotensin II infusion (490 ng/kg min(-1) × 2 weeks) was blunted in adenovirus encoding cre-recombinase-treated mice, as detected by dihydroethidium fluorescence. Deletion of p22(phox) in the SFO eliminated the hypertensive response observed at 2 weeks of angiotensin II infusion compared with control adenovirus encoding red-fluorescent protein-treated mice (mean arterial pressures=97 ± 15 versus 154 ± 6 mm Hg, respectively; P=0.0001). Angiotensin II infusion also promoted marked vascular inflammation, as characterized by accumulation of activated T-cells and other leukocytes, and this was prevented by deletion of the SFO p22(phox). These experiments definitively identify the NADPH oxidases in the SFO as a critical determinant of the blood pressure and vascular inflammatory responses to chronic angiotensin II, and further support a role of reactive oxygen species in central nervous system signaling in hypertension. |
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Authors:
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Heinrich E Lob; David Schultz; Paul J Marvar; Robin L Davisson; David G Harrison |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-12-17 |
Journal Detail:
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Title: Hypertension Volume: 61 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-17 Completed Date: 2013-03-20 Revised Date: 2013-04-25 |
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: 382-7 Citation Subset: IM |
Affiliation:
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Department of Biomedical Sciences, Cornell University, Ithaca, NY, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II Animals Blood Pressure / physiology Hypertension / chemically induced, metabolism*, physiopathology Inflammation / metabolism, physiopathology Integrases / genetics Mice Mice, Transgenic NADPH Oxidase / genetics, metabolism* Oxidation-Reduction Protein Subunits / genetics Reactive Oxygen Species / metabolism Subfornical Organ / metabolism*, physiopathology |
| Grant Support | |
ID/Acronym/Agency:
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P01 GM015431/GM/NIGMS NIH HHS; P01 HL058000/HL/NHLBI NIH HHS; P01 HL095070/HL/NHLBI NIH HHS; P01 HL096571/HL/NHLBI NIH HHS; P01GM015431/GM/NIGMS NIH HHS; P01HL058000/HL/NHLBI NIH HHS; P01HL095070/HL/NHLBI NIH HHS; R01 HL039006/HL/NHLBI NIH HHS; R01 HL063887/HL/NHLBI NIH HHS; R01 HL105294/HL/NHLBI NIH HHS; R01HL039006/HL/NHLBI NIH HHS; R01HL063387/HL/NHLBI NIH HHS; R01HL105294/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Protein Subunits; 0/Reactive Oxygen Species; 11128-99-7/Angiotensin II; EC 1.6.3.1/NADPH Oxidase; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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