Angiotensin 1‐7 modulates electrophysiological characteristics and calcium homoeostasis in pulmonary veins cardiomyocytes via MAS/PI3K/eNOS signalling pathway |
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| Authors: | Yen‐Yu Lu Wen‐Shiann Wu Yung‐Kuo Lin Chen‐Chuan Cheng Yao‐Chang Chen Shih‐Ann Chen Yi‐Jen Chen |
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| Affiliation: | 1. Division of Cardiology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei City, Taiwan;2. School of Medicine, Fu‐Jen Catholic University, New Taipei City, Taiwan;3. Department of Cardiology, Chi‐Mei Medical Center, Tainan, Taiwan;4. Department of Pharmacy, Chia‐Nan University of Pharmacy and Science, Tainan, Taiwan;5. Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;6. Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;7. Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan;8. School of Medicine, Division of Cardiology and Cardiovascular Research Center, Veterans General Hospital‐Taipei, National Yang‐Ming University, Taipei, Taiwan;9. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan |
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| Abstract: | 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 (Ca2+) 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 Ca2+ 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 Ca2+ and Na+‐Ca2+ exchanger currents, but did not affect the voltage‐dependent Na+ current in PV cardiomyocytes. In addition, Ang‐(1‐7) decreased intracellular Ca2+ transient and sarcoplasmic reticulum Ca2+ 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 Ca2+ homoeostasis via Mas/PI3K/eNOS signalling pathway. |
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| Keywords: | angiotensin‐(1‐7) calcium homoeostasis electrophysiology pulmonary vein |
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