Atrial fibrillation (AF) is the most frequent arrhythmia found in clinical practice. In recent studies a decrease in the development or recurrence of AF was found in patients with hypertension treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor-blocking agents (ARBs). Hypertension is related to an increased wall tension in the atria resulting in increased stretch of the individual myocyte which is one of the major stimuli for the remodeling process. In the present study, we used a model of cultured atrial neonatal rat cardiomyocytes under conditions of stretch to provide insight in the mechanisms of the preventive effect of the ARB losartan against AF on a molecular level. Stretch induced a significant increase in protein/DNA ratio and ANF mRNA expression indicating hypertrophy. Expression of genes encoding for I_K1 (Kir2.1 and Kir2.3) as well as I_Kur (Kv1.5) were significantly increased. In contrast, mRNA expression of Kv4.2 was significantly reduced in stretched myocytes. The alterations on the level of gene expression correlated with the corresponding current densities. I_K1 and I_Kur density was significantly increased in stretched myocytes, while Ito density was reduced. These alterations resulted in a significant abbreviation of the action potential duration. Treatment of stretched myocytes with the ARB losartan (1µM) prevented stretch induced increases in protein/DNA ratio and ANP mRNA expression. Concomitantly, the stretch induced alterations in I_K1, I_Kur and I_to density and gene expression were attenuated in the presence of losartan. This prevented the stretch induced abbreviation of the action potential duration. Prevention of stretch induced electrical remodeling might contribute to the clinical effects of losartan against atrial fibrillation.