Intracellular and extracellular angiotensin II enhance the L-type calcium current in the failing heart. Hypertension 44: 360–364

Abstract—The influence of intracellular and extracellular angiotensin II (Ang II) on the L-type calcium current of cardiomyocytes isolated from cardiomyopathic hamsters was investigated. The results indicated that Ang II (108 mmol/L), added to the bath, increased the peak inward calcium current (ICa) density by 373.4 % (P0.05), an effect that depends on the activation of protein kinase C. Intracellular administration of the same dose of Ang II (108 mmol/L) also elicited an increase of peak ICa density but enhanced the rate of ICa inactivation, an effect not seen with extracellular Ang II. Moreover, in control animals, no change in the rate of ICa inactivation was seen with intracellular Ang II. Thapsigargin (1 mol/L), a potent inhibitor of sarcoplasmic reticulum (SR) ATPase, which depletes the SR, decreased the rate of ICa inactivation elicited by intracellular Ang II, although the cytoplasmic calcium concentration was highly buffered with 10 mmol/L EGTA. These findings might indicate that intracellular Ang II releases calcium from the SR and inactivates ICa. The effect of intracellular Ang II on peak ICa was not altered by extracellular losartan (107 mmol/L), supporting the notion that the peptide acted intracellularly. Other studies showed that intracellular Ang I administration (108 mmol/L) enhanced the peak ICa density and the rate of ICa inactivation, an effect that was reduced by intracellular enalaprilat (108 mmol/L). Moreover, intracellular enalaprilat by itself reduced the peak ICa density. These observations might indicate that endogenous Ang II is contributing to ICa modulation in the failing heart. (Hypertension. 2004;44:360-364.) Key Words: angiotensin heart failure calcium curren