Losartan inhibits hyposmotic-induced increase of IKs current and shortening of action potential duration in guinea pig atrial myocytes

Objective: The present study aims to investigate the effect of losartan, an selective angiotensin II type 1 receptor (AT1R) blocker, on both the increase of IKs current and shortening of action potential duration (APD) induced by stretch of atrial myocytes, and to uncover the mechanism underlying the treatment of fibrillation (AF) by AT1R blockers. Methods: Hyposmotic solution (Hypo-S) was applied in the guinea pig atrial myocytes to simulate cell stretch, then patch-clamp technique was applied to record the IKs and APD in atrial myocytes. Results: Hypo-S increased the IKs by 105.6%, while Hypo-S+1-20 μM of losartan only increased the IKs by 70.3-75.5% (p<0.05 vs. Hypo-S). Meanwhile, Hypo-S shortened APD90 by 20.2%, while Hypo-S+1-20 μM of losartan shortened APD90 by 13.03-14.56% (p<0.05 vs. Hypo-S). Conclusion: The above data indicate that the effect of losartan on the electrophysiological changes induced by stretch of atrial myocytes is associated with blocking of AT1 receptor, and is beneficial for the treatment of AF that is often accompanied by the expansion of atrial myocytes and the increase of effective refractory period.