Published Online
on August 2, 2004

A more recent version of this article appeared on September 1, 2004

This Article Full Text (PDF) All Versions of this Article: 44/3/360    most recent 01.HYP.0000139914.52686.74v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Mello, W. C. Articles by Monterrubio, J. Search for Related Content PubMed PubMed Citation Articles by De Mello, W. C. Articles by Monterrubio, J. Related Collections Congestive Cardiovascular Pharmacology ACE/Angiotension receptors Other hypertension

Submitted on May 13, 2004
Revised on June 2, 2004

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

Walmor C. De Mello^* and Jose Monterrubio

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

^* To whom correspondence should be addressed. E-mail: wmello{at}rcm.upr.edu.

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 (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

This article has been cited by other articles:

				G. Michael, L. Xiao, X.-Y. Qi, D. Dobrev, and S. Nattel Remodelling of cardiac repolarization: how homeostatic responses can lead to arrhythmogenesis Cardiovasc Res, February 15, 2009; 81(3): 491 - 499. [Abstract] [Full Text] [PDF]

				V. P. Singh, K. M. Baker, and R. Kumar Activation of the intracellular renin-angiotensin system in cardiac fibroblasts by high glucose: role in extracellular matrix production Am J Physiol Heart Circ Physiol, April 1, 2008; 294(4): H1675 - H1684. [Abstract] [Full Text] [PDF]

				C.-T. Tsai, D. L. Wang, W.-P. Chen, J.-J. Hwang, C.-S. Hsieh, K.-L. Hsu, C.-D. Tseng, L.-P. Lai, Y.-Z. Tseng, F.-T. Chiang, et al. Angiotensin II Increases Expression of {alpha}1C Subunit of L-Type Calcium Channel Through a Reactive Oxygen Species and cAMP Response Element-Binding Protein-Dependent Pathway in HL-1 Myocytes Circ. Res., May 25, 2007; 100(10): 1476 - 1485. [Abstract] [Full Text] [PDF]

				G. Tolstykh, P. M. de Paula, and S. Mifflin Voltage-Dependent Calcium Currents Are Enhanced in Nucleus of the Solitary Tract Neurons Isolated From Renal Wrap Hypertensive Rats Hypertension, May 1, 2007; 49(5): 1163 - 1169. [Abstract] [Full Text] [PDF]

				Y.-L. Li and H. D. Schultz Enhanced sensitivity of Kv channels to hypoxia in the rabbit carotid body in heart failure: role of angiotensin II J. Physiol., August 15, 2006; 575(1): 215 - 227. [Abstract] [Full Text] [PDF]

				J. R. Ehrlich, S. H. Hohnloser, and S. Nattel Role of angiotensin system and effects of its inhibition in atrial fibrillation: clinical and experimental evidence Eur. Heart J., March 1, 2006; 27(5): 512 - 518. [Abstract] [Full Text] [PDF]