Journal article
Loss of bradykinin signaling does not accelerate the development of cardiac dysfunction in type 1 diabetic akita mice
Endocrinology (Philadelphia), Vol.151(8), pp.3536-3542
08/2010
DOI: 10.1210/en.2010-0256
PMCID: PMC2940524
PMID: 20501666
Abstract
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.
Details
- Title: Subtitle
- Loss of bradykinin signaling does not accelerate the development of cardiac dysfunction in type 1 diabetic akita mice
- Creators
- Adam R Wende - Program in Molecular Medicine and Division of Endocrinology, Metabolism, and Diabetes, University of Utah, School of Medicine, Salt Lake City, Utah 84112, USAJamie SotoCurtis D OlsenKarla M P PiresJohn C SchellFrederic Larrieu-LahargueSheldon E LitwinMasao KakokiNobuyuki TakahashiOliver SmithiesE Dale Abel
- Resource Type
- Journal article
- Publication Details
- Endocrinology (Philadelphia), Vol.151(8), pp.3536-3542
- Publisher
- United States
- DOI
- 10.1210/en.2010-0256
- PMID
- 20501666
- PMCID
- PMC2940524
- ISSN
- 0013-7227
- eISSN
- 1945-7170
- Grant note
- R01 HL049277 / NHLBI NIH HHS R01 HL049277-19 / NHLBI NIH HHS UO1 HL087947 / NHLBI NIH HHS T32 HL007576 / NHLBI NIH HHS R01 HL049277-17 / NHLBI NIH HHS U01 HL087947 / NHLBI NIH HHS 5T32HL007576 / NHLBI NIH HHS UO1 DK076131 / NIDDK NIH HHS R01 HL049277-18 / NHLBI NIH HHS R01 HL049277-16 / NHLBI NIH HHS U01 DK076131 / NIDDK NIH HHS
- Language
- English
- Date published
- 08/2010
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984024541602771
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