AJP - Heart and Circulatory Physiology, Vol 270, Issue 3 857-H868, Copyright © 1996 by American Physiological Society

ARTICLES

Modulation of Ca2+ transients in neonatal and adult rat cardiomyocytes by angiotensin II and endothelin-1

R. M. Touyz, J. Fareh, G. Thibault, B. Tolloczko, R. Lariviere and E. L. Schiffrin
Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.

Vasoactive peptides may exert inotropic and chronotropic effects in cardiac muscle by modulating intracellular calcium. This study assesses effects of angiotensin II (ANG II) and endothelin-1 (ET-1) on intracellular free calcium concentration ([Ca2+]i) in cultured cardiomyocytes from neonatal and adult rats. [Ca2+]i was measured microphotometrically and by digital imaging using fura 2 methodology. Receptor subtypes through which these agonists induce responses were determined pharmacologically and by radioligand binding studies. ANG II and ET-1 increased neonatal atrial and ventricular cell [Ca2+]i transients in a dose-dependent manner. ANG II (10(-11) to 10(-7) M) failed to elicit [Ca2+]i responses in adult cardiomyocytes, whereas ET-1 increased [Ca2+]i in a dose-dependent manner. The ETA receptor antagonist BQ-123 significantly reduced (P < 0.05) ET-1 induced responses, and the ETB receptor agonist IRL-1620 (10(-7) to 10(-5) M) significantly increased (P < 0.05) [Ca2+]i in neonatal and adult cardiomyocytes. ET-1 binding studies demonstrated 85% displacement by BQ-123 and approximately 15% by the ETB receptor agonist sarafotoxin S6c, suggesting a predominance of ETA receptors. Competition binding studies for ANG II failed to demonstrate significant binding on adult ventricular myocytes, indicating the absence or presence of very few ANG II receptors. These data demonstrate that ANG II and ET-1 have stimulatory [Ca2+]i effects on neonatal cardiomyocytes, whereas in adult cardiomyocytes, ANG II-induced effects are insignificant, and only ET-1-induced responses, which are mediated predominantly via ETA receptors, are preserved. Cardiomyocyte responses to vasoactive peptides may thus vary with cardiac development.

This article has been cited by other articles:

				T. Nagy, V. Champattanachai, R. B. Marchase, and J. C. Chatham Glucosamine inhibits angiotensin II-induced cytoplasmic Ca2+ elevation in neonatal cardiomyocytes via protein-associated O-linked N-acetylglucosamine Am J Physiol Cell Physiol, January 1, 2006; 290(1): C57 - C65. [Abstract] [Full Text] [PDF]

				D. L. Hunton, L. Zou, Y. Pang, and R. B. Marchase Adult rat cardiomyocytes exhibit capacitative calcium entry Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H1124 - H1132. [Abstract] [Full Text] [PDF]

				L. J. De Windt, H. W. Lim, S. Haq, T. Force, and J. D. Molkentin Calcineurin Promotes Protein Kinase C and c-Jun NH2-terminal Kinase Activation in the Heart. CROSS-TALK BETWEEN CARDIAC HYPERTROPHIC SIGNALING PATHWAYS J. Biol. Chem., April 28, 2000; 275(18): 13571 - 13579. [Abstract] [Full Text] [PDF]

				T. Taigen, L. J. De Windt, H. W. Lim, and J. D. Molkentin Targeted inhibition of calcineurin prevents agonist-induced cardiomyocyte hypertrophy PNAS, February 1, 2000; 97(3): 1196 - 1201. [Abstract] [Full Text] [PDF]

				J. S. Danetz, H. F. Clemo, R. D. Davies, R. P. Embrey, R. J. Damiano Jr, and C. M. Baumgarten AGE-RELATED EFFECTS OF ST THOMAS’ HOSPITAL CARDIOPLEGIC SOLUTION ON ISOLATED CARDIOMYOCYTE CELL VOLUME J. Thorac. Cardiovasc. Surg., September 1, 1999; 118(3): 467 - 476. [Abstract] [Full Text] [PDF]

				K. Onishi, M. Ohno, W. C. Little, and C.-P. Cheng Endogenous Endothelin-1 Depresses Left Ventricular Systolic and Diastolic Performance in Congestive Heart Failure J. Pharmacol. Exp. Ther., March 1, 1999; 288(3): 1214 - 1222. [Abstract] [Full Text]

				J. Fareh, R. M. Touyz, E. L. Schiffrin, and G. Thibault Cardiac Type-1 Angiotensin II Receptor Status in Deoxycorticosterone Acetate–Salt Hypertension in Rats Hypertension, November 1, 1997; 30(5): 1253 - 1259. [Abstract] [Full Text]

				D. Methot, M. C. LaPointe, R. M. Touyz, X.-P. Yang, O. A. Carretero, C. F. Deschepper, E. L. Schiffrin, G. Thibault, and T. L. Reudelhuber Tissue Targeting of Angiotensin Peptides J. Biol. Chem., May 16, 1997; 272(20): 12994 - 12999. [Abstract] [Full Text] [PDF]

				R. M. Touyz, J. Fareh, G. Thibault, and E. L. Schiffrin Intracellular Ca2+ Modulation by Angiotensin II and Endothelin-1 in Cardiomyocytes and Fibroblasts From Hypertrophied Hearts of Spontaneously Hypertensive Rats Hypertension, November 1, 1996; 28(5): 797 - 805. [Abstract] [Full Text]

				C. F. Deschepper, S. Picard, G. Thibault, R. Touyz, and J.-L. Rouleau Characterization of myocardium, isolated cardiomyocytes, and blood pressure in WKHA and WKY rats Am J Physiol Heart Circ Physiol, January 1, 2002; 282(1): H149 - H155. [Abstract] [Full Text] [PDF]

				T. Kakita, K. Hasegawa, E. Iwai-Kanai, S. Adachi, T. Morimoto, H. Wada, T. Kawamura, T. Yanazume, and S. Sasayama Calcineurin Pathway Is Required for Endothelin-1-Mediated Protection Against Oxidant Stress-Induced Apoptosis in Cardiac Myocytes Circ. Res., June 22, 2001; 88(12): 1239 - 1246. [Abstract] [Full Text] [PDF]