Angiotensin II and angiotensin II receptor blocker modulate the arrhythmogenic activity of pulmonary veins.
Angiotensin II receptor blockers (AIIRBs) have been shown to prevent atrial fibrillation. The pulmonary veins (PVs) are the most important focus for the generation of atrial fibrillation. The aim of this study was to evaluate whether angiotensin II or AIIRB may change the arrhythmogenic activity of the PVs. Conventional microelectrodes and whole-cell patch clamps were used to investigate the action potentials (APs) and ionic currents in isolated rabbit PV tissue and single cardiomyocytes before and after administering angiotensin II or losartan (AIIRB). In the tissue preparations, angiotensin II induced delayed after-depolarizations (1, 10, and 100 nM) and accelerated the automatic rhythm (10 and 100 nM). Angiotensin II (100 nM) prolonged the AP duration and increased the contractile force (10 and 100 nM). Losartan (1 and 10 microM) inhibited the automatic rhythm. Losartan (10 microM) prolonged the AP duration and reduced the contractile force (1 and 10 microM). Angiotensin II reduced the transient outward potassium current (I(to)) but increased the L-type calcium, delayed rectifier potassium (I(K)), transient inward (I(ti)), pacemaker, and Na(+)-Ca(2+) exchanger (NCX) currents in the PV cardiomyocytes. Losartan decreased the I(to), I(K), I(ti), and NCX currents. In conclusion, angiotensin II and AIIRB modulate the PV electrical activity, which may play a role in the pathophysiology of atrial fibrillation.
Chen
Yi-Jen
YJ
Division of Cardiovascular Medicine, Taipei Medical University, Wan-Fang Hospital, 111, Hsin-Lung Road, Sec. 3, Taipei 116, Taiwan. a9900112@ms15.hinet.net
Chen
Yao-Chang
YC
Tai
Ching-Tai
CT
Yeh
Hung-I
HI
Lin
Cheng-I
CI
Chen
Shih-Ann
SA
D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004594:Electrophysiology; D019808:Losartan / Q000494:pharmacology; D011667:Pulmonary Veins / Q000187:drug effects*; D011817:Rabbits
D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D000889:Anti-Arrhythmia Agents; D000804:Angiotensin II; D019808:Losartan