Intracellular angiotensin II regulates the inward calcium current in cardiac myocytes

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 [Sar1Val5Ala8] 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 I(Ca). Zaprinast (100 μmol/L), an inhibitor of cGMP phosphodiesterase, when added to the bath solution increases 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 [Sar1Val5Ala8] 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.