Irbesartan-mediated AT1 receptor blockade attenuates hyposmotic-induced enhancement of I Ks current and prevents shortening of action potential duration in atrial myocytes.

<bold>Introduction: </bold>Stretch of the atrial membrane upregulates the slow component of delayed rectifier K(+) current (I(Ks)). Blockade of angiotensin II subtype 1 receptors (AT(1)R) attenuates this increase in I(Ks). The present study aimed to examine the effects of irbesartan, a selective AT(1)R blocker (ABR), on both the enhancement of I(Ks) and the shortening of action potential duration (APD) induced by stretching atrial myocytes for exploring the mechanisms underlying the prevention of atrial fibrillation (AF) by ABR.<bold>Methods: </bold>Hyposmotic solution (Hypo-S) was used to stretch guinea pig atrial myocytes. I(Ks) and APD were recorded using the whole-cell patch-clamp technique.<bold>Results: </bold>Irbesartan (1-50 μM) attenuated the Hypo-S-induced increase in I(Ks) and shortening of APD90. Hypo-S increased the I(Ks) by 113.4%, whereas Hypo-S + 1 μM irbesartan and Hypo-S + 50 μM irbesartan increased the I(Ks) by only 74.5% and 70.3%, respectively. In addition, Hypo-S shortened the APD(90) by 19.0%, whereas Hypo-S + 1 μM irbesartan and Hypo-S + 50 μM irbesartan shortened the APD90 by 12.1% and 12.0%, respectively.<bold>Conclusion: </bold>The actions of irbesartan on electrical changes induced by stretching atrial myocytes are associated with blocking AT(1)R. These actions may be beneficial for treating AF. [ABSTRACT FROM AUTHOR]