Effects of angiotensin ii on cultured rat renomedullary
interstitial cells are mediated by at1a receptors.
Maric, Christine, G. Peter Aldred, Arianne M. Antoine, Rachael G.
Dean, Eveline Eitle, Frederick A. O. Mendelsohn, David A. Williams,
Peter J. Harris, Daine Alcorn.
Departments of Anatomy and Cell Biology, Medicine Austin and
Repatriation Medical Centre and Physiology, The University of
Melbourne, Parkville, 3052, Victoria, Australia
APStracts 3:0138F, 1996.
Renomedullary interstitial cells (RMICs) are prominent in the inner
medullary interstitium and have binding sites for several vasoactive
agents, including ANG II. Although the functional role of RMICs
remains largely unknown, it is likely that the interaction between
RMICs and vasoactive peptides is important in the regulation of renal
function. The current investigation characterizes the cellular
responses following treatment of RMICs with ANG II. Studies were
performed on RMICs isolated from Sprague-Dawley rat kidneys. 125I
-[Sar1, Ile8] ANG II specifically bound to RMICs, at sites determined
by RT-PCR to be of the AT1A subtype. ANG II (10-6 and 10-10 M) had no
effect on either basal or forskolin-stimulated cAMP accumulation in
RMICs, but increased intracellular IP3 concentration after 10 seconds
and intracellular calcium concentration after 18 seconds. For RMICs
plated at low densities, ANG II (10-6 M) induced an increase in
[3H]thymidine incorporation, mediated through the AT1 receptor
subtype. For RMICs plated at high densities, ANG II (10-6 M) induced
an increase in extracellular matrix synthesis as detected by Trans
-[35S] incorporation, an effect also mediated by AT1 receptors. We
conclude that ANG II AT1A receptors on cultured RMICs are coupled to
intracellular second messenger pathways leading to hyperplasia and
synthesis of extracellular matrix.
Received 11 March 1996; accepted in final form 28 July 1996.
APS Manuscript Number F84-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996