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European Journal of Heart Failure 2008 10(12):1172-1176; doi:10.1016/j.ejheart.2008.09.014
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© 2008 European Society of Cardiology

Direct pro-arrhythmogenic effects of angiotensin II can be suppressed by AT1 receptor blockade in human atrial myocardium

Dirk von Lewinskia,*,1, Jens Kockskämpera,1, Sven-Ulrich Rübertusb, Danan Zhub, Jan D. Schmittoc, Friedrich A. Schöndubec, Gerd Hasenfussb and Burkert Pieskea

a Department of Cardiology, Medical University Graz Graz, Austria
b Department of Cardiology and Pneumology, Georg-August-University Göttingen, Germany
c Department of Thoracic and Cardiovascular Surgery, Georg-August-University Göttingen, Germany

* Corresponding author. Abteilung Kardiologie, Medizinische Universität Graz, Auenbruggerplatz 15, 8036 Graz, Austria. Tel.: +43 316 385 2544; fax: +43 316 385 3733. E-mail address: dirk.von-lewinski{at}meduni-graz.at (D. von Lewinski).


  Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Indirect evidence from clinical trials demonstrates that chronic inhibition of the renin–angiotensin-system (RAS) significantly reduces the incidence of AF. Since mechanisms of this protective effect of RAS-blockade are poorly understood, we directly tested proarrhythmic effects of angiotensin II (Ang II) in human atrial myocardium.

Methods: Isolated trabeculae from human atrial appendages (n = 80) were electrically stimulated. We assessed isometric force and incidence of arrhythmic extra contractions (AECs) with and without increasing concentrations of Ang II (1–1000 nmol/L) in the absence or presence of receptor-blockade by saralasin (non-specific ATR-antagonist), irbesartan (AT1R-antagonist) or PD123319 (AT2R-antagonist).

Results: Twitch force and AECs concentration-dependently increased with Ang II. Effects became significant at concentrations >1 nmol/L Ang II and were maximal at 1000 nmol/L (increase in twitch force to 157±14% and AECs from 0 to 80%) saralasin and irbesartan partially prevented the inotropic effect of 100 nmol/L Ang II (by 4±12% and 68±6%; p<0.05), and completely prevented the occurrence of AECs.

Conclusion: Ang II exerts direct pro-arrhythmic effects in human atrial myocardium. These effects are mediated by AT1-receptors and can be prevented by AT1R-blockade. This mechanism may contribute to the beneficial effects of RAS-blockade on AF in clinical trials.

Key Words: Atrial fibrillation • Heart failure • Angiotensin • Remodelling

Received February 1, 2008; Revised June 9, 2008; Accepted September 22, 2008

1 These authors contributed equally.


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