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https://irlib.pccu.edu.tw/handle/987654321/32089
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| 题名: | Leptin decreases heart rate associated with increased ventricular repolarization via its receptor |
| 作者: | Lin, Yen-Chang
Huang, Jianying
Hileman, Stan
Martin, Karen H.
Hull, Robert
Davis, Mary
Yu, Han-Gang |
| 贡献者: | 生科所 |
| 关键词: | leptin
leptin receptor
resting heart rate
QT interval |
| 日期: | 2015-12 |
| 上传时间: | 2016-02-26 11:09:32 (UTC+8) |
| 摘要: | Leptin has been proposed to modulate cardiac electrical properties via beta-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1-30 mu g/kg) decreased resting heart rate; at high doses (150-300 mu g/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03-0.3 mu g/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of beta-adrenergic receptor stimulation. During inhibition of beta-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias. |
| 關聯: | AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 卷: 309 期: 10 頁碼: H1731-H1739 |
| 显示于类别: | [生物科技研究所 ] 期刊論文
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