| Loss of bradykinin signaling does not accelerate the development of cardiac dysfunction in type 1 diabetic akita mice. | |
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MedLine Citation:
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PMID: 20501666 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bradykinin signaling has been proposed to play either protective or deleterious roles in the development of cardiac dysfunction in response to various pathological stimuli. To further define the role of bradykinin signaling in the diabetic heart, we examined cardiac function in mice with genetic ablation of both bradykinin B1 and B2 receptors (B1RB2R(-/-)) in the context of the Akita model of insulin-deficient type 1 diabetes (Ins2(Akita/+)). In 5-month-old diabetic and nondiabetic, wild-type and B1RB2R(-/-) mice, in vivo cardiac contractile function was determined by left-ventricular (LV) catheterization and echocardiography. Reactive oxygen species levels were measured by 2'-7'-dichlorofluorescein diacetate fluorescence. Mitochondrial function and ATP synthesis were determined in saponin-permeabilized cardiac fibers. LV systolic pressure and the peak rate of LV pressure rise and decline were decreased with diabetes but did not deteriorate further with loss of bradykinin signaling. Wall thinning and reduced ejection fractions in Akita mouse hearts were partially attenuated by B1RB2R deficiency, although other parameters of LV function were unaffected. Loss of bradykinin signaling did not increase fibrosis in Ins2(Akita/+) diabetic mouse hearts. Mitochondrial dysfunction was not exacerbated by B1RB2R deficiency, nor was there any additional increase in tissue levels of reactive oxygen species. Thus, loss of bradykinin B2 receptor signaling does not abrogate the previously reported beneficial effect of inhibition of B1 receptor signaling. In conclusion, complete loss of bradykinin expression does not worsen cardiac function or increase myocardial fibrosis in diabetes. |
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Authors:
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Adam R Wende; Jamie Soto; Curtis D Olsen; Karla M P Pires; John C Schell; Frederic Larrieu-Lahargue; Sheldon E Litwin; Masao Kakoki; Nobuyuki Takahashi; Oliver Smithies; E Dale Abel |
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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: 2010-05-25 |
Journal Detail:
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Title: Endocrinology Volume: 151 ISSN: 1945-7170 ISO Abbreviation: Endocrinology Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-27 Completed Date: 2010-09-08 Revised Date: 2011-10-24 |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
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Languages: eng Pagination: 3536-42 Citation Subset: AIM; IM |
Affiliation:
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Program in Molecular Medicine and Division of Endocrinology, Metabolism, and Diabetes, University of Utah, School of Medicine, Salt Lake City, Utah 84112, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bradykinin / metabolism, physiology* Diabetes Mellitus, Experimental / complications*, genetics, metabolism, physiopathology Diabetes Mellitus, Type 1 / complications*, genetics, metabolism, physiopathology Female Heart / physiopathology Heart Diseases / etiology*, genetics, physiopathology Male Mice Mice, Inbred C57BL Mice, Transgenic Mitochondria, Heart / pathology, physiology Myocardium / pathology Oxidative Stress / genetics Receptor, Bradykinin B1 / deficiency, genetics Receptor, Bradykinin B2 / deficiency, genetics Signal Transduction / genetics Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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5T32HL007576/HL/NHLBI NIH HHS; R01 HL049277-16/HL/NHLBI NIH HHS; R01 HL049277-17/HL/NHLBI NIH HHS; R01 HL049277-18/HL/NHLBI NIH HHS; R01 HL049277-19/HL/NHLBI NIH HHS; UO1 DK076131/DK/NIDDK NIH HHS; UO1 HL087947/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptor, Bradykinin B1; 0/Receptor, Bradykinin B2; 58-82-2/Bradykinin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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