Modulation of ca2+ transients in neonatal and adult rat
cardiomyocytes by angiotensin ii and endothelin-1.
Touyz, R. M., J. Fareh, G. Thibault, B. Tolloczko*, R. Larivi[PHI]re,
E. L. Schiffrin.
MRC Multidisciplinary Research Group on Hypertension, Clinical
Research Institute of Montreal, University of Montreal and CF
Research Laboratory, Montreal Chest Hospital Research Center, McGill
University
APStracts 2:0451H, 1995.
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 - 10-7 mol/l)
failed to elicit [Ca2+]i responses in adult cardiomyocytes whereas
ET-1 increased [Ca2+]i in a dose-dependent manner (pD2 7.2 ( 0.34).
The ETA receptor antagonist, BQ-123, significantly reduced
(p<0.05) ET-1-induced responses and the ETB receptor agonist,
IRL-1620 (10-7 - 10-5 mol/l), 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.
Received 21 February 1995; accepted in final form 29 August 1995.
APS Manuscript Number H158-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95