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IR@PKUHSC  > 北京大学第三临床医学院  > 心血管内科  > 期刊论文
学科主题: 临床医学
题名:
Distinct actions of intermittent and sustained beta-adrenoceptor stimulation on cardiac remodeling
作者: Ma XiaoWei1,3; Song Yao1,3; Chen Chao1,3; Fu YongNan1,3; Shen Qiang2,3; Li ZiJian1,3; Zhang YouYi1,3
关键词: beta-adrenoceptor ; reactive oxygen species ; NADPH oxidase ; cardiac hypertrophy ; cardiac fibrosis
刊名: SCIENCE CHINA-LIFE SCIENCES
发表日期: 2011-06-01
DOI: 10.1007/s11427-011-4183-9
卷: 54, 期:6, 页:493-501
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biology
研究领域[WOS]: Life Sciences & Biomedicine - Other Topics
关键词[WOS]: RAT VENTRICULAR MYOCYTES ; HEART-FAILURE ; OXIDATIVE STRESS ; IN-VIVO ; ALPHA(1)-ADRENERGIC RECEPTOR ; BLOOD-PRESSURE ; S6 KINASE ; HYPERTROPHY ; ISOPROTERENOL ; ACTIVATION
英文摘要:

Heart disease is associated with increased sympathetic nerve activity and elevated levels of circulating catecholamines, resulting in chronic stimulation of the beta-adrenergic receptors (beta-AR) and consequent pathological cardiac remodeling. Experimentally, chronic administration of the beta-AR agonist isoproterenol (ISO) has been most commonly used to model beta-AR-induced cardiac remodeling. However, it remains unclear whether beta-AR-mediated cardiac remodeling and dysfunction differs between sustained versus pulsatile (intermittent) exposure to a beta-agonist. Here, we compare the effects of intermittent versus sustained administration of ISO on cardiac remodeling and function in mice. Animals were administered 5 mg (kg d)(-1) ISO for 2 weeks either by daily subcutaneous injection, or continuous infusion via an implanted osmotic minipump. Cardiac function and remodeling were determined by echocardiography, micromanometry and histology. Moreover, Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to define the proteins and genes involved. Both sustained and intermittent administration of ISO resulted in a similar degree of cardiac hypertrophy (16% and 19%, respectively). However, mice receiving ISO by daily injection developed more severe ventricular systolic and diastolic dysfunction and myocardial fibrosis compared with mice receiving ISO via the osmotic minipump. The disparity in results between the delivery methods is suggested to be due, at least in part, to increased expression of fibrogenic factors, including connective tissue growth factor (CTGF) and NADPH oxidase (NOX4), in mice receiving intermittent application of ISO. In summary, compared with sustained exposure to a beta-AR agonist, intermittent beta-AR stimulation leads to more severe cardiac dysfunction and fibrosis. These findings not only further our understanding of beta-AR function in the setting of cardiac pathophysiology, but also highlight that significant differences can result dependent upon the mode of experimental beta-AR stimulation in inducing cardiomyopathy.

语种: 英语
所属项目编号: 2011CB503903 ; 81030001 ; 30971161 ; 30910103902
项目资助者: National Basic Research Program of China ; National Natural Science Foundation of China ; International Cooperation and Exchange of the National Natural Science Foundation of China
WOS记录号: WOS:000292050500001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61856
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

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作者单位: 1.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 3, Inst Vasc Med, Beijing 100191, Peoples R China
3.Peking Univ, Inst Cardiovasc Sci, Beijing 100191, Peoples R China

Recommended Citation:
Ma XiaoWei,Song Yao,Chen Chao,et al. Distinct actions of intermittent and sustained beta-adrenoceptor stimulation on cardiac remodeling[J]. SCIENCE CHINA-LIFE SCIENCES,2011,54(6):493-501.
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