Intracellular Angiotensin II Regulates the Inward Calcium Current in Cardiac Myocytes

Abstract

Abstract —The influence of intracellular administration of angiotensin II (Ang II) on the inward calcium current (I Ca ) was investigated in single myocytes isolated from adult rat ventricle. Comparative studies were also made in ventricular cells of Golden hamsters. The I Ca was measured in single cells using the whole-cell voltage clamp configuration. The results indicated that Ang II (10 −8 mmol/L) dialyzed into the rat myocytes reduced the peak I Ca by 35±5.5% (n=20; P <0.05). Losartan (10 −7 mmol/L) added to the bath did not suppress the effects of Ang II, indicating that the peptide is acting intracellularly. Moreover, the intracellular dialysis of losartan (10 −6 mmol/L) or [Sar 1 Val 5 Ala 8 ] Ang II (10 −6 mmol/L) did not change the effect of Ang II. Stimulation of I Ca by exogenous cAMP or inhibition of protein kinase C did not alter the effect of Ang II on I Ca . Zaprinast (100 μmol/L), an inhibitor of cGMP phosphodiesterase, when added to the bath solution increased appreciably the effect of Ang II on I Ca ( P <0.05). In ventricular myocytes of Golden hamsters, in which Ang II has a positive inotropic action, the intracellular administration of Ang II (10 −8 mmol/L) increased I Ca by 36±2.4% (n=20; P >0.05). The effect of the peptide was not altered by the intracellular administration of losartan (10 −6 mmol/L), by [Sar 1 Val 5 Ala 8 ] Ang II (10 −6 mmol/L), or by the inhibitor of protein kinase A. The inhibition of protein kinase C, however, prevented the effect of Ang II I Ca in the hamster myocytes. The results particularly suggest that the activation of the cardiac renin-angiotensin system regulates I Ca and myocardial contractility, an effect that varies with the species.