Role of the endogenous renin-angiotensin system on stretch-induced
c-fos gene activation and pkc- translocation in intact adult rat
hearts.
Kang, Peter M., Antonio Nakouzi, Timothy Simpson, James Scheuer, and
Peter M. Buttrick.
Division of Cardiology, Albert Einstein College of
Medicine/Montefiore Medical Center, Bronx, NY 10467
APStracts 2:0486H, 1995.
Myocardial stretch and the renin-angiotensin system (RAS) have both
been implicated in the development of cardiac hypertrophy through the
activation of specific target genes. However, the relative importance
of these putative hypertrophic stimuli has not been established in
vivo. We studied this using an isolated isovolumic heart preparation
in which coronary perfusion pressure (CPP), left ventricular end
-diastolic pressure (LVEDP), and pharmacologic therapy can be
independently manipulated. High CPP (140 cm H20), which increased
coronary flow (8.99 vs 17.6 ml/min) and LV systolic pressure (50 vs
91 mmHg), increased steady state c-fos mRNA expression 2.3 fold (all
p < 0.01 vs low CPP). In contrast, increased LVEDP (25 mmHg) and/or
infusion of angiotensin II in the absence of increased CPP was not
associated with an increase in c-fos mRNA expression. The change in
c-fos gene expression seen with increased CPP was largely reversed by
treatment with an angiotensin II type 1 (AT1) receptor blocker.
Hearts perfused at high CPP had increased translocation/activation of
protein kinase C (PKC)- relative to controls. None of the hearts
studied were ischemic during perfusion. Thus, in the perfused adult
rat heart, dynamic but not static stretch activates the early
response gene, c-fos, and may involve the endogenous RAS and PKC.
Received 16 May 1995; accepted in final form 9 October 1995.
APS Manuscript Number H464-5.
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