Cell swelling, impulse conduction, and cardiac arrhythmias in the failing heart. Opposite effects of angiotensin 11 and angiotensin (1-7) on cell volume regulation

The influence of hypotonic solution on cell volume and electrophysiology properties of the failing heart of cardiomyopathic hamsters (TO-2) was investigated. The results showed an increase in cell volume of quiescent isolated ventricular myocytes by 66% within 30 min. Angiotensin (1-7) [Ang (1-7)] (10(-8) M) administered to isotonic solution, elicited a gradual decline in cell volume and a significant decrease of the swelling-activated chloride current (I(Clswell)). The effect of Ang (1-7) on cell volume was inhibited by ouabain (10(-7) M). Angiotensin 11 (10-8 M) caused cell swelling and increased I(Clswell). Experiments performed on isolated left ventricles of cardiomyopathic hamsters at an advanced stage of the disease, indicated that hypotonic solution prepared by diluting the normal Krebs solution by 25%, showed a gradual decrease of conduction velocity, generation of early after depolarizations and block of impulse conduction within 10 min. Implications to myocardial ischemia are discussed.