From the Department of Internal Medicine II, Yokohama City University
School of Medicine, Yokohama (K.T., S.U., Y.S., N.N., S.K., T.I., M.K., M.I.);
Lead Generation Research Laboratories, Tanabe Seiyaku Co, Ltd, Osaka (T.S.);
and the Institute of Applied Biochemistry (A.F., K.M.) and Gene Experiment
Center (H.M.), University of Tsukuba, Ibaraki, Japan.
Correspondence to Kouichi Tamura, MD, Department of Internal Medicine II, Yokohama City University School of Medicine, 3–9, Fukuura, Kanazawa-ku, Yokohama 236, Japan. E-mail tamukou{at}yellow.med.yokohama-cu.ac.jp
Abstract—This study examined
expression of renin-angiotensin system (RAS) component
mRNAs in angiotensinogen gene knockout
(Atg-/-) mice. Wild-type (Atg+/+) and
Atg-/- mice were fed a normal-salt (0.3% NaCl) or
high-salt (4% NaCl) diet for 2 weeks. Angiotensinogen,
renin, angiotensin-converting enzyme (ACE),
angiotensin II type 1a receptor (AT1A), and
angiotensin II type 2 receptor (AT2) mRNA
levels were measured by Northern blot analysis. In
Atg+/+ mice, activities of circulating RAS and renal
angiotensinogen mRNA level were decreased by salt loading,
whereas levels of renal and cardiac ACE; renal, brain, and cardiac
AT1A; and brain and cardiac AT2 mRNA were
increased by salt loading. Although activities of circulating RAS were
not detected in Atg-/- mice, salt loading increased
blood pressure in Atg-/- mice. In
Atg-/- mice, renal renin mRNA level was decreased by
salt loading; in contrast, salt loading increased renal
AT1A and cardiac AT2 mRNA levels in
Atg-/- mice, and these activated levels in
Atg-/- mice were higher than those in
Atg+/+ mice fed the high-salt diet. Thus, expression of
each component of the RAS is regulated in a tissue-specific manner that
is distinct from other components of systemic and local RAS and that
appears to be mediated by a mechanism other than changes in the
circulating or tissue levels of angiotensin peptides.
© 1998 American Heart Association, Inc.
Scientific Contributions
Effect of Genetic Deficiency of Angiotensinogen on the Renin-Angiotensin System
Key Words: renin-angiotensin system • angiotensinogen • angiotensin-converting enzyme • receptors, angiotensin • RNA, messenger • sodium, dietary
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