Intracellular angiotensin II regulates the inward calcium current in cardiac myocytes

The influence of intracellular administration of angiotensin II (Ang LI) 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 mu mol/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 LT (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.