Trophic effects of angiotensin ii on neonatal rat cardiac myocytes
are mediated by cardiac fibroblasts.
Kim, Noel N., Francisco J. Villarreal, Morton P. Printz, Ann A. Lee,
and Wolfgang H. Dillmann.
Departments of Medicine and Pharmacology, University of California,
San Diego, San Diego, California 92103-8412
APStracts 2:0083E, 1995.
Cultured neonatal rat cardiac fibroblasts (NF) and myocytes (NM) were
used to examine the distribution of Ang-II receptors and the
potential role of NF in mediating the trophic response to Ang-II in
the heart. In NM preparations cultured for 2 - 5 days, specific
binding to [125I]Ang-II was <10% of the specific binding in
cultured NF. Binding assays,immunocytochemistry and autoradiography
in NM cultured for >5 days identified two populations of cells; one
with fibroblast-like morphology and high density of Ang-II receptors
and another with low binding, comparable to NM cultures at day 5 or
earlier. Conditioned media (CM) from untreated NF increased cell
surface area and net [3H]leu incorporation 1.4 fold in NM. CM from
Ang-II treated NF enhanced [3H]leu incorporation 2.2 fold in NM. This
potentiating effect of Ang-II was inhibited by losartan and was
absent when Ang-II was added directly to NM. In addition, studies
using antibodies and bioassay for TGF-[beta]1 suggested that TGF
-[beta]1 does not mediate the trophic effects of Ang-II on NM. We
conclude that Ang-II receptors are localized predominantly on NF and
that Ang-II can indirectly stimulate hypertrophy of NM by stimulating
NF to produce a transferrable factor(s). These data suggest that
cardiac fibroblasts may play a critical role in mediating the
hypertrophic response to Ang-II in the rat heart.
Received 5 December 1994; accepted in final form 7 April 1995.
APS Manuscript Number E506-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 April 1995.