血管紧张素 1-7 通过 MAS/PI3K/eNOS 信号通路调节肺静脉心肌细胞的电生理特性和钙稳态。
Angiotensin 1-7 modulates electrophysiological characteristics and calcium homoeostasis in pulmonary veins cardiomyocytes via MAS/PI3K/eNOS signalling pathway.
机构信息
Division of Cardiology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei City, Taiwan.
School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
出版信息
Eur J Clin Invest. 2018 Jan;48(1). doi: 10.1111/eci.12854. Epub 2017 Dec 5.
BACKGROUND
Atrial fibrillation (AF) is the most common sustained arrhythmia, and pulmonary veins (PVs) play a critical role in triggering AF. Angiotensin (Ang)-(1-7) regulates calcium (Ca ) homoeostasis and also plays a critical role in cardiovascular pathophysiology. However, the role of Ang-(1-7) in PV arrhythmogenesis remains unclear.
MATERIALS AND METHODS
Conventional microelectrodes, whole-cell patch-clamp and the fluo-3 fluorimetric ratio technique were used to record ionic currents and intracellular Ca in isolated rabbit PV preparations and in single isolated PV cardiomyocytes, before and after administration of Ang-(1-7).
RESULTS
Ang (1-7) concentration dependently (0.1, 1, 10 and 100 nmol/L) decreased PV spontaneous electrical activity. Ang-(1-7) (100 nmol/L) decreased the late sodium (Na ), L-type Ca and Na -Ca exchanger currents, but did not affect the voltage-dependent Na current in PV cardiomyocytes. In addition, Ang-(1-7) decreased intracellular Ca transient and sarcoplasmic reticulum Ca content in PV cardiomyocytes. A779 (a Mas receptor blocker, 3 μmol/L), L-NAME (a NO synthesis inhibitor, 100 μmol/L) or wortmannin (a specific PI3K inhibitor, 10 nmol/L) attenuated the effects of Ang-(1-7) (100 nmol/L) on PV spontaneous electric activity.
CONCLUSION
Ang-(1-7) regulates PV electrophysiological characteristics and Ca homoeostasis via Mas/PI3K/eNOS signalling pathway.
背景
心房颤动（AF）是最常见的持续性心律失常，肺静脉（PVs）在触发 AF 中起着关键作用。血管紧张素（Ang）-（1-7）调节钙（Ca）稳态，在心血管病理生理学中也起着关键作用。然而，Ang-（1-7）在 PV 心律失常发生中的作用尚不清楚。
材料和方法
使用常规微电极、全细胞膜片钳和 fluo-3 荧光比色技术，在给予 Ang-（1-7）前后，记录分离的兔 PV 标本和单个分离的 PV 心肌细胞中的离子电流和细胞内 Ca。
结果
Ang（1-7）浓度依赖性（0.1、1、10 和 100 nmol/L）降低 PV 自发性电活动。Ang-（1-7）（100 nmol/L）降低晚期钠（Na）、L 型 Ca 和 Na-Ca 交换体电流，但不影响 PV 心肌细胞中的电压依赖性 Na 电流。此外，Ang-（1-7）降低了 PV 心肌细胞中的细胞内 Ca 瞬变和肌浆网 Ca 含量。A779（Mas 受体阻滞剂，3 μmol/L）、L-NAME（NO 合成抑制剂，100 μmol/L）或 wortmannin（PI3K 特异性抑制剂，10 nmol/L）减弱了 Ang-（1-7）（100 nmol/L）对 PV 自发性电活动的影响。
结论
Ang-（1-7）通过 Mas/PI3K/eNOS 信号通路调节 PV 电生理特性和 Ca 稳态。
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