| NADPH oxidase contributes to coronary endothelial dysfunction in the failing heart. | |
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MedLine Citation:
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PMID: 19168727 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Increased reactive oxygen species (ROS) produced by the failing heart can react with nitric oxide (NO), thereby decreasing NO bioavailability. This study tested the hypothesis that increased ROS generation contributes to coronary endothelial dysfunction in the failing heart. Congestive heart failure (CHF) was produced in six dogs by ventricular pacing at 240 beats/min for 4 wk. Studies were performed at rest and during treadmill exercise under control conditions and after treatment with the NADPH oxidase inhibitor and antioxidant apocynin (4 mg/kg iv). Apocynin caused no significant changes in heart rate, aortic pressure, left ventricular (LV) systolic pressure, LV end-diastolic pressure, or maximum rate of LV pressure increase at rest or during exercise in normal or CHF dogs. Apocynin caused no change in coronary blood flow (CBF) in normal dogs but increased CBF at rest and during exercise in animals with CHF (P < 0.05). Intracoronary ACh caused dose-dependent increases of CBF that were blunted in CHF. Apocynin had no effect on the response to ACh in normal dogs but augmented the response to ACh in CHF dogs (P < 0.05). The oxidative stress markers nitrotyrosine and 4-hydroxy-2-nonenal were significantly greater in failing than in normal myocardium. Furthermore, coelenterazine chemiluminescence for O(2)(-) was more than twice normal in failing myocardium, and this difference was abolished by apocynin. Western blot analysis of myocardial lysates demonstrated that the p47(phox) and p22(phox) subunits of NADPH were significantly increased in the failing hearts, while real-time PCR demonstrated that Nox2 mRNA was significantly increased. The data indicate that increased ROS generation in the failing heart is associated with coronary endothelial dysfunction and suggest that NADPH oxidase may contribute to this abnormality. |
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Authors:
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Ping Zhang; Mingxiao Hou; Yunfang Li; Xin Xu; Michel Barsoum; Yingjie Chen; Robert J Bache |
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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: 2009-01-23 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 296 ISSN: 0363-6135 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-03-03 Completed Date: 2009-04-09 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H840-6 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of Minnesota Health Sciences Center, Minneapolis, MN 55455, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetophenones
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pharmacology Acetylcholine / pharmacology Aldehydes / metabolism Animals Antioxidants / pharmacology Cardiac Pacing, Artificial Coronary Circulation Coronary Vessels / drug effects, enzymology*, physiopathology Disease Models, Animal Dogs Dose-Response Relationship, Drug Endothelium, Vascular / drug effects, enzymology*, physiopathology Enzyme Inhibitors / pharmacology Female Heart Failure / enzymology*, physiopathology Hemodynamics Male NADPH Oxidase / antagonists & inhibitors, genetics, metabolism* Oxidative Stress RNA, Messenger / metabolism Superoxides / metabolism* Tyrosine / analogs & derivatives, metabolism Up-Regulation Vasodilation / drug effects* Vasodilator Agents / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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HL-20598/HL/NHLBI NIH HHS; HL-21872/HL/NHLBI NIH HHS; HL-71790/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Acetophenones; 0/Aldehydes; 0/Antioxidants; 0/Enzyme Inhibitors; 0/RNA, Messenger; 0/Vasodilator Agents; 11062-77-4/Superoxides; 29343-52-0/4-hydroxy-2-nonenal; 3604-79-3/3-nitrotyrosine; 498-02-2/acetovanillone; 51-84-3/Acetylcholine; 55520-40-6/Tyrosine; EC 1.6.3.1/NADPH Oxidase; EC 1.6.3.1/neutrophil cytosolic factor 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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