doi: 10.1161/CIRCULATIONAHA.106.640854
(Circulation. 2006;114:e566.)
© 2006 American Heart Association, Inc.
Correspondence |
Response to Letter Regarding Article, "Angiotensin II Potentiates the Slow Component of Delayed Rectifier K+ Current via the AT1 Receptor in Guinea Pig Atrial Myocytes"
Department of Physiology, Shiga University of Medical Science, Shiga, Japan
Central Research Laboratory, Shiga University of Medical Science, Shiga, Japan
Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Shiga, Japan
We thank Dr Christ and his colleagues very much for their interest in our article.1 We attempted to contend that the short-term enhancement of atrial IKs by angiotensin II (Ang II) shortens the action potential duration (APD) and may contribute to the very early phase of atrial electrical remodeling. We fully agree that the antifibrotic effects may represent the principal mechanism by which Ang II type 1 receptor blockers prevent atrial fibrillation (AF), but the difference between short-term and long-term phases of atrial remodeling should also be considered.
Dr Christ and colleagues cited a rapid pacing of the right atrium in a canine model used to induce long-term atrial structural remodeling and increased susceptibility to AF.2 The animals were treated with candesartan from 1 week before the start of pacing, and the treatment was continued for 5 weeks. Although candesartan prevented structural remodeling and susceptibility to AF, it failed to affect the changes in atrial effective refractory period (AERP) produced by atrial tachycardia. On the other hand, the same authors3 examined the effect of candesartan on short-term changes in AERP produced by rapid atrial pacing for just 180 minutes. The AERP shortening was completely prevented by candesartan, demonstrating a role for Ang II type 1 receptors in the early stage of electrical remodeling. In humans, irbesartan was found to significantly suppress the recurrence of AF.4 The AF recurrence was efficiently inhibited during early days but not at more than 14 days. The most straightforward interpretation of the data would be that irbesartan did not prevent the development of atrial fibrosis but regressed the electrical remodeling. Our study, which examined the immediate action of Ang II and Ang II type 1 receptor blockers on a specific ion current regulating the APD, is consistent with a role for Ang II in early electrical remodeling.
In the studies of human atrial myocytes by Bertaso et al and Wang et al5,6 cited by Dr Christ et al, the myocytes were isolated by using the "chunk" method, which has previously been demonstrated to be associated with damage to delayed rectifier currents.7 Thus, we cannot take the absence of IKs from patch-clamp recordings of isolated human atrial myocytes as evidence of their lack of contribution to atrial repolarization in humans. Moreover, gain-of-function mutations of KCNQ1 are known to cause familial AF.8 We therefore think that upregulation of human atrial IKs should be of substantial contribution in generating the AF, in which the shortening of APD is at least 1 of the major determinants of AF maintenance.
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Disclosures
None.
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References |
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 Top References |
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