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Effects of Adrenomedullin on Atrial Electrophysiology and Pulmonary Vein Arrhythmogenesis

Authors :
Chye-Gen Chin
Ahmed Moustafa Elimam
Fong-Jhih Lin
Yao-Chang Chen
Yung-Kuo Lin
Yen-Yu Lu
Satoshi Higa
Shih-Ann Chen
Ming-Hsiung Hsieh
Yi-Jen Chen
Source :
International Journal of Molecular Sciences, Vol 23, Iss 22, p 14064 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Adrenomedullin, a peptide with vasodilatory, natriuretic, and diuretic effects, may be a novel agent for treating heart failure. Heart failure is associated with an increased risk of atrial fibrillation (AF), but the effects of adrenomedullin on atrial arrhythmogenesis remain unclear. This study investigated whether adrenomedullin modulates the electrophysiology of the atria (AF substrate) or pulmonary vein (PV; AF trigger) arrhythmogenesis. Conventional microelectrode or whole-cell patch clamps were used to study the effects of adrenomedullin (10, 30, and 100 pg/mL) on the electrical activity, mechanical response, and ionic currents of isolated rabbit PV and sinoatrial node tissue preparations and single PV cardiomyocytes. At 30 and 100 pg/mL, adrenomedullin significantly reduced the spontaneous beating rate of the PVs from 2.0 ± 0.4 to 1.3 ± 0.5 and 1.1 ± 0.5 Hz (reductions of 32.9% ± 7.1% and 44.9 ± 8.4%), respectively, and reduced PV diastolic tension by 12.8% ± 4.1% and 14.5% ± 4.1%, respectively. By contrast, adrenomedullin did not affect sinoatrial node beating. In the presence of L-NAME (a nitric oxide synthesis inhibitor, 100 μM), adrenomedullin (30 pg/mL) did not affect the spontaneous beating rate or diastolic tension of the PVs. In the single-cell experiments, adrenomedullin (30 pg/mL) significantly reduced the L-type calcium current (ICa-L) and reverse-mode current of the sodium–calcium exchanger (NCX). Adrenomedullin reduces spontaneous PV activity and PV diastolic tension by reducing ICa-L and NCX current and thus may be useful for treating atrial tachyarrhythmia.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
23
Issue :
22
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.81af91e518434690b1978751500cdee6
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms232214064