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(Hypertension. 2004;44:360.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Intracellular and Extracellular Angiotensin II Enhance the L-Type Calcium Current in the Failing Heart

From the Department of Pharmacology (W.C.D.M.) and Institute of Neurobiology (J.M.), Medical Sciences Campus, University of Puerto Rico, San Juan.

Correspondence to Dr Walmor C. De Mello, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00936-5067. E-mail wmello{at}rcm.upr.edu

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 (10^–8 mmol/L), added to the bath, increased the peak inward calcium current (I_Ca) density by 37±3.4% (P<0.05), an effect that depends on the activation of protein kinase C. Intracellular administration of the same dose of Ang II (10^–8 mmol/L) also elicited an increase of peak I_Ca density but enhanced the rate of I_Ca inactivation, an effect not seen with extracellular Ang II. Moreover, in control animals, no change in the rate of I_Ca inactivation was seen with intracellular Ang II. Thapsigargin (1 µmol/L), a potent inhibitor of sarcoplasmic reticulum (SR) ATPase, which depletes the SR, decreased the rate of I_Ca 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 I_Ca. The effect of intracellular Ang II on peak I_Ca was not altered by extracellular losartan (10^–7 mmol/L), supporting the notion that the peptide acted intracellularly. Other studies showed that intracellular Ang I administration (10^–8 mmol/L) enhanced the peak I_Ca density and the rate of I_Ca inactivation, an effect that was reduced by intracellular enalaprilat (10^–8 mmol/L). Moreover, intracellular enalaprilat by itself reduced the peak I_Ca density. These observations might indicate that endogenous Ang II is contributing to I_Ca modulation in the failing heart.

Key Words: angiotensin • heart failure • calcium current

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