UNLABELLED: 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 45+/-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.
UNLABELLED: 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 45+/-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.
Authors: Alicia C Reid; Jacqueline A Brazin; Christopher Morrey; Randi B Silver; Roberto Levi Journal: Curr Pharm Des Date: 2011-11 Impact factor: 3.116
Authors: T Horio; M Akiyama; Y Iwashima; F Yoshihara; S Nakamura; T Tokudome; M Okutsu; H Tanaka; I Komatsubara; N Okimoto; S Kamakura; Y Kawano Journal: J Hum Hypertens Date: 2016-12-29 Impact factor: 3.012
Authors: Renita E Horton; Moran Yadid; Megan L McCain; Sean P Sheehy; Francesco S Pasqualini; Sung-Jin Park; Alexander Cho; Patrick Campbell; Kevin Kit Parker Journal: PLoS One Date: 2016-01-25 Impact factor: 3.240