AJP - Cell Physiology, Vol 263, Issue 4 C838-C850, Copyright © 1992 by American Physiological Society
Intracardiac detection of angiotensinogen and renin: a localized renin-angiotensin system in neonatal rat heart
D. E. Dostal, K. N. Rothblum, M. I. Chernin, G. R. Cooper and K. M. Baker
Weis Center for Research, Geisinger Clinic, Danville 17822.
There is increasing evidence that the renin-angiotensin system (RAS)
modulates cardiovascular function through both blood-borne and
tissue-derived components. The existence of a local RAS has been proposed
in the heart based on biochemical and molecular biological studies that
identify angiotensinogen and renin. We conducted the present study to
determine the chamber localization of angiotensinogen and renin mRNA in
neonatal rat heart and whether these components could be identified in
cultured cardiomyocytes and fibroblasts obtained from neonatal rat heart.
Experiments using polymerase chain reaction (PCR) indicated that whole
hearts obtained from neonatal rats contained both angiotensinogen and renin
mRNA. With the use of radiolabeled cDNA probes and in situ hybridization,
angiotensinogen and renin transcripts were localized both in the atria and
ventricles of neonatal rat hearts. Relative signal strengths for
angiotensinogen were highest in the left and right ventricles. In contrast,
renin signal strength was overall much lower and preferentially localized
in the left ventricle. To investigate the cellular source of
angiotensinogen and renin, cultured neonatal heart cardiomyocytes and
ventricular fibroblasts were screened for angiotensinogen and renin
messenger RNA and protein using PCR and indirect immunofluorescent
staining, respectively. These experiments demonstrated that both cell types
produce transcripts and the respective translation products for
angiotensinogen and renin. These data suggest that the site of angiotensin
II synthesis can occur at the level of the individual cardiomyocyte and
fibroblast, where it may serve to directly and/or indirectly regulate
cardiac rate, force, growth, and development in the neonate.
