A repolarizing conduction in the heart augmented by hyposmotic or mechanically induced membrane stretch is the slow component of delayed rectifier K(+) current (I (Ks)). I (Ks) upregulation is recognized as a factor promoting appearance of atrial fibrillation (AF) since gain-of-function mutations of the channel genes have been detected in congenital AF. Mechanical stretch activates angiotensin II type 1 (AT(1)) receptor in the absence of its physiological ligand angiotensin II. We investigated the functional role of AT(1) receptor in I (Ks) enhancement in hyposmotically challenged guinea pig atrial myocytes using the whole-cell patch-clamp method. In atrial myocytes exposed to hyposmotic solution with osmolality decreased to 70% of the physiological level, I (Ks) was enhanced by 84.1%, the duration of action potential at 90% repolarization (APD(90)) was decreased by 16.8%, and resting membrane potential was depolarized (+4.9 mV). The hyposmotic-induced effects on I (Ks) and APD(90) were significantly attenuated by specific AT(1) receptor antagonist candesartan (1 and 5 muM). Pretreatment of atrial myocytes with protein tyrosine kinase inhibitors tyrphostin A23 and A25 suppressed but the presence of tyrosine phosphatase inhibitor orthovanadate augmented hyposmotic stimulation of I (Ks). The above results implicate AT(1) receptor and tyrosine kinases in the hyposmotic modulation of atrial I (Ks) and suggest acute antiarrhythmic properties of AT(1) antagonists in the settings of stretch-related atrial tachyarrhythmias.