Proliferation-associated changes in angiotensin ii receptor density
and calcium handling in aortic myocytes from spontaneously
hypertensive rats.
C[circumflex]ortes, Steyner De F., Virginia S. Lemos, Catherine
Corriu, and Jean-Claude Stoclet.
Laboratoire de Pharmacologie et Physiopathologie Cellulaires,
Universit[acute]e Louis Pasteur de Strasbourg, URA CNRS 600.
Facult[acute]e de Pharmacie, BP 24, F-67401 Illkirch - Cedex,
France
APStracts 3:0261H, 1996.
The aim of the present work was to characterize angiotensin II (Ang
II) receptors and their effect on intracellular free calcium
concentration ([Ca2+]i) in proliferating aortic smooth muscle cells
(VSMCs) from spontaneously hypertensive (SHR) and normotensive
Wistar-Kyoto (WKY) rats. Independently from the proliferating state
of cultures, the apparent affinities of ligands (Ang II >
losartan >> CGP 42112A) were consistent with the presence
of AT1 receptors in primary cells from both SHR and WKY rats. In
proliferating cultures, the increases in [Ca2+]i elicited by Ang II
(100 nM) were dramatically attenuated or abolished in VSMCs from both
strains, compared to confluent and post-confluent cultures. Calcium
releases induced by ionomycin and by Ang II in the absence of
extracellular calcium were also impaired in proliferating cultures.
In addition, no significant strain difference was found in
proliferating cultures with respect to Ang II receptors density,
basal [Ca2+]i and Ang II-induced increases in [Ca2+]i. However, Ang
II receptors density significantly increased in SHR but not in WKY
VSMCs at post-confluence. Furthermore, basal [Ca2+]i was elevated in
confluent and post-confluent cultures from SHR but not in those from
WKY. In confluent cultures, both Ang II- and ionomycin-induced Ca2+
releases were enhanced in SHR VSMCs, compared to WKY. These results
show that Ang II-induced Ca2+ release and ionomycin-sensitive calcium
stores are enhanced in SHR VSMCs, but dramatically decreased in
proliferating VSMCs cultures from both strains. The mechanisms
underlying these alterations remain to be defined. However, the
results suggest that alterations in Ang II AT1 receptors density and
in intracellular calcium handling found in confluent and post
-confluent cultures are not associated with the proliferative
phenotype of SHR VSMCs. In addition, no evidence for any change in
the Ang II receptor subtype associated with proliferation of VSMCs
was found in both strains.
Received 27 February 1996; accepted in final form 21 May 1996.
APS Manuscript Number H195-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96