Intracellular angiotensin-(1–12) changes the electrical properties of intact cardiac muscle

Abstract

In the present work, the influence of intracellular injection of angiotensin-(1–12) [Ang-(1–12)] on the electrical properties of the intact left ventricle of Wistar Kyoto rats was investigated with electrophysiological methods. Particular attention was given to the role of chymostatin on the effect of the peptide. The results indicated that intracellular administration of the peptide elicited a depolarization of the surface cell membrane and an increase of duration of the action potential followed by the generation of early afterdepolarizations. The increment of action potential duration caused by Ang-(1–12) (100 nM) was due to a decrease of total potassium current recorded from single cardiomyocytes using the whole cell configuration of pCAMP. The decrease of potassium current was related to the activation of protein kinase C (PKC) because the specific inhibitor of kinase C, Bis-1 (10⁻⁹ M), abolished Ang-(1–12) effects on the potassium current. The question of whether the effect of Ang-(1–12) was related to the formation of Ang II by chymase was investigated.The results revealed that the intracellular administration of chymostatin, a chymase inhibitor (10⁻⁹ M) abolished the effect of intracellular Ang-(1–12) on the potassium current. Moreover, intracellular Ang II (100 nM), by itself, reduced the potassium current, an effect decreased by intracellular valsartan (100 nM). Valsartan (10–9 M) dialyzed into the cell abolished the effect of Ang-(1–12) (100 nM). These observations demonstrate that the effect of Ang-(1–12) on potassium current was related to the formation of Ang II and that the peptide has arrhythmogenic properties.