title: Pressure overload induces cardiac hypertrophy in angiotensin II type 1A receptor knockout mice.
abstract: BACKGROUND
  Many studies have suggested that the renin-angiotensin system plays an important role in the development of pressure overload-induced cardiac hypertrophy. Moreover, it has been reported that pressure overload-induced cardiac hypertrophy is completely prevented by ACE inhibitors in vivo and that the stored angiotensin II (Ang II) is released from cardiac myocytes in response to mechanical stretch and induces cardiomyocyte hypertrophy through the Ang II type 1 receptor (AT1) in vitro. These results suggest that the AT1-mediated signaling is critical for the development of mechanical stress-induced cardiac hypertrophy.
  
  
  RESULTS
  To determine whether AT1-mediated signaling is indispensable for the development of pressure overload-induced cardiac hypertrophy, pressure overload was produced by constricting the abdominal aorta of AT1A knockout (KO) mice. Quantitative reverse transcriptase-polymerase chain reaction revealed that the cardiac AT1 (probably AT1B) mRNA levels in AT1A KO mice were <10% of those of wild-type (WT) mice and were not affected by pressure overload. Chronic treatment with subpressor doses of Ang II increased left ventricular mass in WT mice but not in KO mice. Pressure overload, however, fully induced cardiac hypertrophy in KO as well as WT mice. There were no significant differences between WT and KO mice in expression levels of fetal-type cardiac genes, in the left ventricular wall thickness and systolic function as revealed by the transthoracic echocardiogram, or in the histological changes such as myocyte hypertrophy and fibrosis.
  
  
  CONCLUSIONS
  AT1-mediated Ang II signaling is not essential for the development of pressure overload-induced cardiac hypertrophy.
authors.affiliation: Department of Medicine III, University of Tokyo School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Harada
authors.forename: I
authors.initials: I
authors.lastname: Komuro
authors.forename: I
authors.initials: I
authors.lastname: Shiojima
authors.forename: D
authors.initials: D
authors.lastname: Hayashi
authors.forename: S
authors.initials: S
authors.lastname: Kudoh
authors.forename: T
authors.initials: T
authors.lastname: Mizuno
authors.forename: K
authors.initials: K
authors.lastname: Kijima
authors.forename: H
authors.initials: H
authors.lastname: Matsubara
authors.forename: T
authors.initials: T
authors.lastname: Sugaya
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: Y
authors.initials: Y
authors.lastname: Yazaki
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D004452:Echocardiography; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D000804:Angiotensin II