Angiotensin-converting enzyme inhibitors regulate the na+-k+ pump
via effects on angiotensin metabolism.
Hool, Livia C., David F. Gray, Bruce G. Robinson, and Helge H.
Rasmussen.
Departments of Cardiology and Molecular Genetics, Kolling Institute
of Medical Research, Royal North Shore Hospital, St. Leonards, and
University of Sydney, Sydney, New South Wales 2065; and School of
Biological Sciences, Macquarie University, North Ryde, Sydney, New
South Wales 2109, Australia
APStracts 3:0044C, 1996.
Treatment of rabbits with angiotensin-converting enzyme inhibiting
drugs (ACE-inhibitors) increases Na+-K+ pump current (Ip) of isolated
cardiac myocytes when intracellular Na+ is at near-physiological
levels. To examine if effects of ACE-inhibitors are related to
angiotensin metabolism, we measured Ip in myocytes isolated from
rabbits treated with the AT1 receptor antagonist losartan. Ip was
increased to levels similar to those after treatment with ACE
-inhibitors. Exposure of myocytes from captopril treated rabbits to 10
nM angiotensin II (Ang II) for 45 min in vitro reduced Ip to levels
similar to those of myocytes from untreated control rabbits. This
rapid response to Ang II suggests that treatment with captopril had
induced a functional change in preexisting pump units rather than
synthesis of a new population of pumps. Consistent with this we could
not detect a change in Na+-K+ pump subunit mRNAs during treatment
with captopril. The decrease in Ip of myocytes from captopril treated
rabbits induced by Ang II in vitro was blocked by pertussis toxin,
bisindolylmaleimide I and staurosporine. Exposure of myocytes to
phorbol, 12-myristate, 13-acetate induced a decrease in Ip similar to
that induced by Ang II. Thus, ACE-inhibitors regulate the Na+-K+ pump
in myocytes via an effect on angiotensin metabolism. The regulatory
mechanism appears to include the AT1 receptor, a G protein and
protein kinase C.
Received 24 January 1995; accepted in final form 22 January 1996.
APS Manuscript Number C44-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96