Identification and activation of the autocrine renin-angiotensin
system in adult ventricular myocytes in vivo.
Zhang, Xun, David E. Dostal, Krzysztof Reiss, Wei Cheng, Jan Kajstura,
Peng Li, Harer Huang, Edmund H. Sonnenblick, Leonard G. Meggs,
Kenneth M. Baker, and Piero Anversa.
Department of Medicine, New York Medical College, Valhalla, New
York; the Division of Cardiology, Department of Medicine, Albert
Einstein College of Medicine, New York; and The Weis Center for
Research, Geisinger Clinic, Danville, PA
APStracts 2:0211H, 1995.
To date, the demonstration that the molecular components of the renin
-angiotensin system (RAS) are present in adult ventricular myocytes is
lacking. In addition, whether the RAS is upregulated under conditions
of overload and myocyte hypertrophy in vivo remains to be determined.
By employing an in vivo model of ischemic cardiomyopathy in rats, we
document that adult myocytes express the genes for renin,
angiotensinogen, angiotensin converting enzyme (ACE) and angiotensin
II (Ang II) receptors. Moreover, renin, ACE and Ang II receptor mRNAs
increased in stressed myocytes undergoing cellular hypertrophy. At
the protein level, the percentage of myocytes containing renin, Ang I
and Ang II was significantly increased in the overloaded heart. The
number of binding sites for Ang II per myocyte also markedly
increased under this setting. These results provide direct evidence
of the existence of a myocyte RAS which may be activated in
pathologic states of the heart to support myocyte growth and
contractile function.
Received 31 May 1994; accepted in final form 8 May 1995.
APS Manuscript Number H477-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.