Effect of genetic deficiency of angiotensinogen on the renin-angiotensin system.
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 la 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.
Department of Internal Medicine II, Yokohama City University School of Medicine, Yokohama, Japan. tamukou@yellow.med.yokohama-cu.ac.jp
K
K
Tamura
S
S
Umemura
Y
Y
Sumida
N
N
Nyui
S
S
Kobayashi
T
T
Ishigami
M
M
Kihara
T
T
Sugaya
A
A
Fukamizu
H
H
Miyazaki
K
K
Murakami
M
M
Ishii
D000808:Angiotensinogen / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000502:physiology; D005786:Gene Expression Regulation; D006321:Heart / Q000502:physiology; D007668:Kidney / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D011945:Receptors, Angiotensin / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D017673:Sodium Chloride, Dietary; D000808:Angiotensinogen